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Objective: To investigate the predictive value of ventricular modified Graeb score (mGS score) combined with serum fibroblast growth factor receptor-1 (FGFR-1) and pentraxin 3 (PTX3) for poor prognosis in patients with intraventricular hemorrhage (IVH) after external ventricular drainage. Methods: 109 patients with IVH who received external ventricular drainage treatment from the First Hospital of Hebei Medical University from February 2020 to February 2022 were selected. Glasgow Outcome Scale score (GOS) was used to evaluate the prognosis of patients at 3 months after discharge. According to GOS score, the patients with IVH were divided into poor prognosis group (51 cases) and good prognosis group (58 cases). The mGS scores were evaluated, and serum FGFR-1 and PTX3 levels were detected before surgery. Multivariate Logistic regression analysis was used to analyze the factors affecting the poor prognosis of patients with IVH after external ventricular drainage. Receiver operating characteristic curve (ROC) was drawn to analyze the value of mGS score combined with serum FGFR-1 and PTX3 in predicting poor prognosis in patients with IVH after external ventricular drainage. Results: The preoperative mGS score and serum PTX3 level in the poor prognosis group were higher than those in the good prognosis group (P＜0.05), and serum FGFR-1 level was lower than that in the good prognosis group (P＜0.05). Complicated with cerebral hernia, high mGS score and high PTX3 were risk factors for poor prognosis in patients with IVH after external ventricular drainage (P＜0.05), and high FGFR-1 was protective factor (P＜0.05). The area under curve of combined mGS score and serum FGFR-1 and PTX3 predicting poor prognosis in patients with IVH after external ventricular drainage was 0.894, which was higher than that predicted by above indicators alone. Conclusion: The mGS score and serum PTX3 level increased, and serum FGFR-1 level decreased in patients of poor prognosis with IVH after external ventricular drainage. Combined mGS score, serum FGFR-1 and PTX3 has high prognostic value in patients with IVH after external ventricular drainage. [ABSTRACT FROM AUTHOR]

Objective: We report here the results of a prospective study of circulating tumor DNA (ctDNA) detection in patients undergoing uveal melanoma (UM) liver metastases resection (NCT02849145). Background: In UM patients, the liver is the most common and often only site of metastases. Local treatments of liver metastases, such as surgical resection, have a likely benefit in selected patients. Methods: Upon enrollment, metastatic UM patients eligible for curative liver surgery had plasma samples collected before and after surgery. GNAQ/GNA11 mutations were identified in archived tumor tissue and used to quantify ctDNA by droplet digital polymerase chain reaction which was then associated with the patient's surgical outcomes. Results: Forty-seven patients were included. Liver surgery was associated with a major increase of cell-free circulating DNA levels, with a peak 2 days after surgery (~20-fold). Among 40 evaluable patients, 14 (35%) had detectable ctDNA before surgery, with a median allelic frequency of 1.1%. These patients experienced statistically shorter relapse-free survival (RFS) versus patients with no detectable ctDNA before surgery (median RFS: 5.5 vs 12.2 months; hazard ratio=2.23, 95% CI: 1.06--4.69, P= 0.04), and had a numerically shorter overall survival (OS) (median OS: 27.0 vs 42.3 months). ctDNA positivity at postsurgery time points was also associated with RFS and OS. Conclusions: This study is the first to report ctDNA detection rate and prognostic impact in UM patients eligible for surgical resection of their liver metastases. If confirmed by further studies in this setting, this noninvasive biomarker could inform treatment decisions in UM patients with liver metastases. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the independent associations between growth differentiation factor 15 (GDF‐15) level at admission and cardiovascular (CV) death, thrombotic events, heart failure (HF), and bleeding outcomes in patients with coronary artery disease (CAD). Methods and results: We measured the plasma concentrations of GDF‐15 centrally in patients from the BIomarker‐based Prognostic Assessment for patients with Stable angina and acute coronary Syndrome (BIPass) registry, which consecutively enrolled patients with CAD from November 2017 to September 2019 at five tertiary hospitals in China. The outcomes included CV death, thrombotic events [myocardial infarction (MI) and ischaemic stroke], HF events [acute HF during hospitalization and hospitalization for HF post‐discharge (A/H HF) and cardiogenic shock], and bleeding outcomes [non‐coronary artery bypass grafting‐related major bleeding and clinically significant bleeding (CSB)] during the 12 month follow‐up period after hospitalization. Among 6322 patients with CAD {65.4% male, median age 63.7 [inter‐quartile range (IQR)] 56.0–70.1 years}, the median concentration of plasma GDF‐15 at admission was 1091 (IQR 790.5–1635.0) ng/L. Higher concentrations of GDF‐15 were associated with an increased risk of CV death [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.35–2.88, P < 0.001], A/H HF (HR 2.69, 95% CI 1.92–3.77, P < 0.001), cardiogenic shock (HR 1.46, 95% CI 1.04–2.05, P = 0.029), and CSB (HR 1.48, 95% CI 1.22–1.79, P < 0.001), but not for MI or stroke, after adjusting for clinical risk factors and prognostic biomarkers. Adding GDF‐15 to the model with risk factors and biomarkers improved the net reclassification for CV death, A/H HF, cardiogenic shock, and CSB. Conclusions: In patients with CAD, admission levels of GDF‐15 were associated with an increased 1 year risk of CV death, HF, and bleeding outcomes, but not with thrombotic events. GDF‐15 may be a prognostic biomarker for CV death, HF, and bleeding outcomes and could be used to refine the risk assessment of these specific clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04044066 [ABSTRACT FROM AUTHOR]

Background: Various tools simpler than the Glasgow Coma Scale (GCS) have been proposed for the assessment of consciousness. In this study, the validity of three coma scales [Simplified Motor Scale, Modified GCS Motor Response, and AVPU (alert, verbal, painful, unresponsive)] is evaluated for the recognition of coma and the prediction of short- and long-term mortality and poor outcome. The predictive validity of these scales is also compared to the GCS. Methods: Patients treated in the Department of Neurosurgery and the Intensive Care Unit in need of consciousness monitoring were assessed by four raters (two consultants, a resident and a nurse) using the GCS. The corresponding values of the simplified scales were estimated. Outcome was recorded at discharge and at 6 months. Areas Under the Receiver Operating Characteristic Curve (AUCs) were calculated for the prediction of mortality and poor outcome, and the identification of coma. Results: Eighty-six patients were included. The simplified scales showed good overall validity (AUCs > 0.720 for all outcomes of interest), but lower than the GCS. For the identification of coma and the prediction of long-term poor outcome, the difference was significant (p < 0.050) for all the ratings of the most experienced rater. The validity of these scales was comparable to the GCS only in predicting in-hospital mortality, but without this being consistent for all raters. Conclusion: The simplified scales showed inferior validity than the GCS. Their potential role in clinical practice needs further investigation. Thus, the replacement of the GCS as the main scale for consciousness assessment cannot be currently supported. [ABSTRACT FROM AUTHOR]

Objectives: A promising cancer-predictive biomarker is the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a comprehensive indicator of nutrition and systemic inflammation. There needs to be more data on the HALP index and EC, and to our knowledge, there is no investigation into how this indicator would have predicted EC in the Turkish population. Methods: In this retrospective study, EC individuals with uterine cancer underwent surgery between January 2010 and December 2020, all data were collected from the hospital records. Results: This retrospective study revealed 163 non-metastatic endometrial cancer (median age was 61, ranging from 41 to 84 years). The mean HALP index was 43 (min 10-max 115). HALP index levels were significantly decreased from FIGO stage I to stage III (mean values were 50, 40, and 27). Lymph node metastasis was detected in 11 patients with significantly lower HALP index compared to lymph node-free patients (30 vs 44, p=0.018). Conclusion: This is the first study in our population we found the HALP index is a good prognostic marker to predict pathologic features for early-stage endometrial cancer. [ABSTRACT FROM AUTHOR]

Background: At the pan-cancer level, exploring the expression and prognostic significance of a gene, such as UBE2S, will help to gain insight into the role of the gene and its feasibility for cancer screening, prognosis assessment and even gene therapy. Methods: The Cancer Genome Atlas, Human Protein Atlas, Kaplan–Meier, Tumor Immunology Estimation Resource and other databases were used to analyze the expression of UBE2S at the pan-cancer level, its prognosis and the role of the immune microenvironment. Immunohistochemistry samples of tumor tissue collected in our clinic were taken as verification. Results: UBE2S is significantly overexpressed in pan-cancer and is closely associated with malignant clinical features, poor prognosis and tumor-associated macrophages. Conclusion: UBE2S may be a potential diagnostic and prognostic marker for pan-cancer and is associated with tumor-associated macrophages. [ABSTRACT FROM AUTHOR]

Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRβ2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. 109 EC patients were included. The expression of the ADRβ2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. ADRβ2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35–8.88)) and overall survival (HR = 2.98 (95%CI:1.40–6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC. • ADRβ2 expression was neither associated with clinico-pathological parameters nor prognostic value in the analyzed patients. • DRD1 expression showed an inverse association with tumor size and stage in our endometrial cancer patient cohort. • DRD2 expression showed significant positive association with non-endometrioid endometrial cancer, high grade and tumor size. • High expression of DRD2 is an independent significant prognostic marker for predicting OS and DFS in the patient's cohort. • DRD1 agonism and DRD2 antagonism combination reduced cellular viability and could have a potential therapeutic benefit. [ABSTRACT FROM AUTHOR]

Lung cancer is the most common cause of cancer-related deaths in the world. One of the reasons of poor prognosis and high mortality of lung cancer patients is the diagnosis of the disease in its advanced stage. Despite innovative diagnostic methods and multiple completed and ongoing clinical trials aiming at therapy improvement, no significant increase in patients' long-term survival has been noted over last decades. Patients would certainly benefit from early detection of lung cancer. Therefore, it is crucial to find new biomarkers that can help predict outcomes and tumor responses in order to maximize therapy effectiveness and avoid over- or under-treating patients with lung cancer. Nowadays, scientists' attention is mainly dedicated to so-called liquid biopsy, which is fully non-invasive and easily available method based on simple blood draw. Among common liquid biopsy elements, circulating tumor nucleic acids are worth mentioning. Epigenetic biomarkers, particularly miRNA expression, have several distinct features that make them promising prognostic markers. In this review, we described miRNA's involvement in tumorigenesis and present it as a predictor of cancer development and progression, potential indicator of treatment efficacy, and most importantly promising therapeutic target. [ABSTRACT FROM AUTHOR]

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Background: Annexins (ANXAs) play a crucial role in the development and progression of tumors. However, their specific involvement in prostate cancer (PCa) remains unclear. Objective: To investigate the function and clinical significance of key ANXAs in PCa. Methods: Multiple databases were used to analyze the expression levels, genetic variations, potential prognostic value and clinical significance of ANXAs in PCa. Then, the co-expressed genes of ANXA6 were identified, and the correlation between ANXA6 and immune cell infiltration was validated using the Tumor Immune Estimation Resource (TIMER) database. Additionally, in vitro assays such as Cell Counting Kit-8 (CCK-8), Colony Formation, Transwell and T-cell Chemotaxis assays were conducted to validate the functions of ANXA6. Moreover, multiple types of in vivo assays were performed to further validate the identified ANXA6 functions. Results: The results demonstrated that ANXA2, ANXA6 and ANXA8 were significantly downregulated in PCa. ANXA6 upregulation was significantly associated with improved PCa patients' overall survival. Enrichment analysis revealed that ANXA6 and its co-expressed genes were involved in tumor progression, and ANXA6 overexpression could effectively inhibit the proliferation, migration and invasion of PC-3 cells. In vivo studies also demonstrated that ANXA6 overexpression suppressed tumor growth. Importantly, ANXA6 was found to promote the chemotaxis of CD4+ T cells and CD8+ T cells towards PC-3 cells, and the overexpression of ANXA6 in PC-3 cells promoted the polarization of macrophages into M1 macrophages in the supernatant of PCa cells. Conclusions: ANXA6 demonstrated promising potential for consideration as a prognostic biomarker in PCa as it was found to play key roles in regulating immune cell infiltration and the malignant progression to PCa. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported the critical roles of tumor cells and the tumor microenvironment in tumor prognosis and immunotherapeutic response. However, how Tenascin-XB (TNXB) expression relates to glioma prognosis and to the levels of tumor-infiltrating immune cells in various cancers has remained elusive. Therefore, this work aimed to investigate the expression, prognostic value, biological function and correlation between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues.Methods: First, we explored TNXB expression in glioma tissues by using online biological databases. Second, we assessed the clinical importance of TNXB expression with chi-squared tests, Cox regression and Kaplan-Meier curve analyses. Third, we examined the relationship between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues in an online database. Additionally, we assessed the associations of TNXB expression with genetic markers of immune cells and common immune-checkpoint molecules.Results: Elevated TNXB expression in glioma tissues correlated with tumor grade, according to several databases. Elevated TNXB expression was significantly associated with negative clinicopathological manifestations and poorer prognosis, on the basis of TCGA (n=510) data. Furthermore, univariate and multivariate Cox regression indicated that TNXB was an independent indicator of glioma prognosis. Pathway enrichment analyses suggested that TNXB participates in the immune response, humoral immune response and interferon-gamma-mediated signaling pathways. Importantly, TNXB expression was significantly associated with higher levels of tumor-infiltrating immune cells in diverse cancers. Furthermore, TNXB expression was strongly associated with genetic markers of immune cells and common immune-checkpoint molecules (e.g., PD-1, PD-L1, CTLA4, TIM-3, LAG3, PDCD1LG2, TIGIT and Siglec-15).Conclusions: TNXB expression correlates with poorer prognosis and higher levels of tumor-infiltrating immune cells in several cancers. In addition, TNXB expression is likely to contribute to the regulation of dendritic cells, exhausted T cells, regulatory T cells and tumor-associated macrophages in gliomas. Consequently, TNXB may serve as an important prognostic marker and may play an immunomodulatory role in tumors.

Abstract Background To develop and validate a predictive nomogram for tumor residue 3–6 months after treatment based on postradiotherapy plasma Epstein–Barr virus (EBV) deoxyribonucleic acid (DNA), clinical stage, and radiotherapy (RT) dose in patients with stage II–IVA nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods In this retrospective study, 1050 eligible patients with stage II–IVA NPC, who completed curative IMRT and underwent pretreatment and postradiotherapy (-7 to +28 days after IMRT) EBV DNA testing, were enrolled from 2012 to 2017. The prognostic value of the residue was explored using Cox regression analysis in patients (n=1050). A nomogram for predicting tumor residues after 3–6 months was developed using logistic regression analyses in the development cohort (n=736) and validated in an internal cohort (n=314). Results Tumor residue was an independent inferior prognostic factor for 5-year overall survival, progression-free survival, locoregional recurrence-free survival and distant metastasis-free survival (all P

Haoran Lu,1,&ast; Rou Zhao,2,&ast; Qianqian Qin,3 Liyong Tang,1 Guodong Ma,1 Baoyu He,2 Jing Liang,2 Li Wei,2 Xutong Wang,2 Qingli Bie,2 Xuning Wang,4 Bin Zhang2,5 1Department of Hepatobiliary Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 3Department of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 4Department of General Surgery, The Air Force Hospital of Northern Theater PLA, Liaoning, People’s Republic of China; 5Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Zhang, Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People’s Republic of China, Tel +86 186 0647 3594, Fax +86 537 2213030, Email zhb861109@163.comBackground: Hepatocellular carcinoma (HCC) is one of the most common type of cancers, but there is still a lack of known biomarkers for the effective diagnosis or prognosis of HCC. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a substrate of protein kinase C, which was located in the cell plasma membrane. The purpose of our study was to evaluate the role of MARCKS in HCC.Methods: The role of MARCKS in HCC was explored by bioinformatics and experiment.Results: We demonstrated that MARCKS expression was significantly elevated in HCC datasets of TCGA. MARCKS was up-regulated in tumor sample in HCC. Functional enrichment indicated that MARCKS-related differentially expressed genes (DEGs) were mainly enriched in cell junction tissue, response to growth factors and cell population proliferation. Tumor and ECM-receptor interactions related pathways were enriched by the KEGG. MARCKS expression in HCC patients was higher in females, younger individuals, and those at worse clinical stages. Cox regression analysis showed that MARCKS expression was a risk factor for overall survival and disease-specific survival of patients.Conclusion: MARCKS was up-regulated in HCC, may play a crucial role in HCCs, and has prognostic value for clinical outcomes.Keywords: myristoylated alanine-rich C-kinase substrate, HCC, TCGA, prognostic value

Abstract Background Cancers harboring spliceosome mutations are highly sensitive to additional perturbations on the spliceosome that leads to the development of onco-therapeutics targeting the spliceosome and opens novel opportunities for managing aggressive tumors lacking effective treatment options such as triple negative breast cancers. Being the core spliceosome associated proteins, SNRPD1 and SNRPE have been both proposed as therapeutic targets for breast cancer management. Yet, their differences regarding their prognostic and therapeutic use as well as roles during carcinogenesis are largely unreported. Methods We conducted in silico analysis at gene expression and genetic levels to differentiate the clinical relevance of SNRPD1 and SNRPE, and explored their differential functionalities and molecular mechanistic associations with cancer in vitro. Results We showed that high SNRPD1 gene expression was prognostic of poor breast cancer survival whereas SNRPE was not. The SNRPD1 expression quantitative trait loci, rs6733100, was found independently prognostic of breast cancer survival using TCGA data. Silencing either SNRPD1 or SNRPE independently suppressed the growth of breast cancer cells, but decreased migration was only observed in SNRPD1-silenced cells. Knocking down SNRPD1 but not SNRPE triggers doxorubicin resistance in triple negative breast cancer cells. Gene enrichment and network analyses revealed the dynamic regulatory role of SNRPD1 on cell cycle and genome stability, and the preventive role of SNRPE against cancer stemness that may neutralize its promotive role on cancer cell proliferation. Conclusion Our results differentiated the functionalities of SNRPD1 and SNRPE at both prognostic and therapeutic levels, and preliminarily explained the driving mechanism that requires additional explorations and validations.

Abstract Background The significance of BRCA alterations has been implicated in the development of metastatic castration‐resistant prostate cancer (PC). The details of the frequency and significance of BRCA alterations in localized PC remain unknown. In this study, we investigated the frequency and clinical significance of BRCA alterations in localized PCs using an in‐house next‐generation sequencer (NGS) system. Methods DNA was extracted from formalin‐fixed paraffin‐embedded tissues of surgical specimens from 126 patients with clinically localized PC who underwent radical prostatectomy. The mutation information of 164 cancer genes was analyzed using the PleSSision‐Rapid test. Both copy number (CN) variation and loss of heterozygosity of various genes, such as BRCA1 and BRCA2, were estimated and reported. Results Next‐generation sequencer analyses revealed that the BRCA2 CN was decreased in 17 patients (13.5%) and the BRCA1 CN in six (4.8%) patients. NGS‐based CN values were shown to be highly correlated with droplet digital PCR‐based CN values. Tissue‐specific BRCA expression investigated using the Human Protein Atlas showed that the decreased CN of BRCA2, but not BRCA1, is responsible for the decreased BRCA activity in PC. Ten of the 22 patients with decreased BRCA2 CN were presumed to have somatic heterozygous deletion. There were no observed associations between the heterozygous deletion of BRCA2 and various clinicopathological parameters. Furthermore, three of 10 patients developed biochemical recurrence within 3 months after surgery. Multivariate analyses revealed that the initial prostate‐specific antigen levels and BRCA2 CN were independent factors for biochemical recurrence. Conclusion Our results suggest that a decrease in BRCA2 CN may be used as a biomarker for predicting recurrence after surgery in localized PC. Early screening for somatic alterations in BRCA2 using NGS may help to broadly predict the risk of PC progression.

Bowen Li,&ast; Jinghang Liu,&ast; Liangzhi Xu, Qi Xu, Zhaohui Liu, Tiande Liu Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiande Liu, Departments of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China, Tel +8613479101447, Email liutd123@163.comBackground: The DNA binding protein NABP2 (nucleic acid binding protein 2) is a member of the SSB (single-stranded DNA-binding) protein family, which is involved in DNA damage repair. Its prognostic significance and relationship with immune infiltration in hepatocellular carcinoma (HCC), however, remain unknown.Methods: The purpose of this study was to estimate the prognostic value of NABP2 and to investigate its possible immune function in HCC. By applying multiple bioinformatics methods, we gathered and analysed data from The Cancer Genome Atlas (TCGA), Cancer Cell Lineage Encyclopedia (CCLE), and Gene Expression Omnibus (GEO) to investigate the potential oncogenic and cancer-promoting role of NABP2, including the differential expression, prognostic value, immune cell infiltration association, and drug sensitivity of NABP2 in HCC. Immunohistochemistry and Western blotting were used to validate the expression of NABP2 in HCC. The knockdown of NABP2 expression by siRNA was further used to validate its role in hepatocellular carcinoma.Results: Our findings indicated that NABP2 was overexpressed in HCC samples and was related to poor survival, clinical stage, and tumour grade in HCC patients. Analysis of functional enrichment indicated that NABP2 was potentially involved in the cell cycle, DNA replication, G2M checkpoint, E2F targets, apoptosis, P53 signalling, TGFA signalling via NF-κB, and so on. NABP2 was shown to be significantly linked to immune cell infiltration and immunological checkpoints in HCC. Analyses of drug sensitivity predict a number of drugs that could potentially be used to target NABP2. Moreover, in vitro experiments verified the promoting effect of NABP2 on the migration and proliferation of hepatocellular carcinoma cells.Conclusion: Based on these findings, NABP2 appears to be a candidate biomarker for HCC prognosis and immunotherapy.Keywords: bioinformatics analysis, NABP2, hepatocellular carcinoma, prognostic value, immune infiltration

Jing Huang,1,2,&ast; Hongjiang Pu,3,&ast; Jintao He,4 Xiaohu Tang5 1The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, People’s Republic of China; 3Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, People’s Republic of China; 4Kunming Medical University, Kunming, People’s Republic of China; 5Department of Rheumatology, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohu Tang, Department of Rheumatology, the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, 120 Guanghua Street, Wuhua District, Kunming, 650032, People’s Republic of China, Tel/Fax +86-871-63639262, Email h.tang0718@163.comBackground: Most cancer-related deaths around the globe are caused by lung cancer. The present treatments for metastatic non-small cell lung cancer (mNSCLC) are cytotoxic chemotherapy (CCT), targeted therapy (TT) and immunotherapy, but the benefit of the same regime varies greatly. Hence, it is important to identify biomarkers to predict the efficacy of modalities. Previous literature suggested certain parameters might be predictive factors. Nevertheless, the utility of these parameters is limited due to the types of solid tumors.Purpose: The study aimed to examine whether the lung immune prognostic index (LIPI) was related to outcomes of CCT, immune checkpoint inhibitors (ICIs) and TT for mNSCLC patients.Materials and Methods: A retrospective cohort study between September 2012 and May 2020 was conducted on 350 Chinese mNSCLC patients, including 147 patients receiving ICIs, 103 TT, and 100 CCT. The data were examined to analyze the prognostic value of LIPI among various treatments.Main Outcomes and Measures: The associations between PFS and good, intermediate, or poor prognostic LIPI scores in ICIs, TT, and CCT were determined, respectively.Results: In univariable analyses, there was a relevance between a good LIPI score and better PFS among patients receiving ICIs (HR, 0.81; 95% CI, 0.44– 1.51), TT (HR, 0.35; 95% CI, 0.16– 1.74), and CCT (HR, 0.39; 95% CI, 0.19– 0.80). In multivariable analyses, the intermediate LIPI score was linked to better PFS only in patients receiving TT (HR, 0.31; 95% CI, 0.17– 0.92) rather than ICIs (HR, 1.12; 95% CI, 0.66– 2.45) or CCT (HR, 1.24; 95% CI, 0.49– 4.55).Conclusion: Baseline LIPI value is an important prognostic biomarker for mNSCLC patients treated with TT. Shorter PFS with TT was associated with poor baseline LIPI. Poor LIPI score may be considered as a promising indicator showing which patients are unlikely to respond well to TT. The prognostic value of LIPI can be more clearly determined through prospective clinical study.Keywords: lung immune prognostic index, metastatic non-small cell lung cancer, prognostic value

Objective: The F-box protein (FBXO) family plays a key role in the malignant progression of tumors. However, the biological functions and clinical value of the FBXO family in liver cancer remain unclear. Our study comprehensively assessed the clinical value of the FBXO family in hepatocellular carcinoma (HCC) and constructed a novel signature based on the FBXO family to predict prognosis and guide precision immunotherapy. Methods: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression characteristics and prognostic value of the FBXO family in HCC. A predictive model based on the FBXO family using TCGA database; and its predictive ability was validated using the ICGC database. Further analyses revealed that this predictive model can independently predict the overall survival (OS) rate of patients with HCC. We further analyzed the association of this predictive model with signaling pathways, clinical pathological features, somatic mutations, and immune therapy responses. Finally, we validated the biological functions of cyclin F (CCNF) through in vitro experiments. Results: A predictive model involving three genes (CCNF, FBXO43, and FBXO45) was constructed, effectively identifying high and low-risk patients with differences in OS, clinicopathological characteristics, somatic mutations, and immune cell infiltration status. Additionally, knock-down of CCNF in HCC cell lines reduced cell proliferation in vitro, suggesting that CCNF may be a potential therapeutic target for HCC. Conclusions: The predictive model based on the FBXO family can effectively predict OS and the immune therapy response in HCC. Additionally, CCNF is a potential therapeutic target for HCC.

BackgroundCirculating tumor cells (CTCs) could serve as a predictive biomarker in breast cancer (BC). Due to its high heterogeneity, the diagnostic and prognostic values of CTC are challenging.MethodsWe searched published studies from the databases of PubMed, Cochrane Library, Embase, and MEDLINE. The detection capability and hazard ratios (HRs) of CTCs were extracted as the clinical diagnosis and prognosis evaluation. Subgroup analyses were divided according to the detection methods, continents, treatment periods, therapeutic plans, and cancer stages.ResultsIn this study, 35 publications had been retrieved with 8,935 patients enrolled. The diagnostic efficacy of CTC detection has 74% sensitivity and 98% specificity. The positive CTC detection (CTC+) would predict worse OS and PFS/DFS in both mid-therapy and post-therapy (HROS, 3.09; 95% CI, 2.17–4.39; HRPFS/DFS, 2.06; 95% CI, 1.72–2.47). Moreover, CTC+ indicated poor survival irrespective of the treatment phases and sampling times (HROS, 2.43; 95% CI, 1.85–3.19; HRPFS/DFS, 1.82; 95% CI, 1.66–1.99). The CTC+ was associated with poor survival regardless of the continents of patients (HROS = 2.43; 95% CI, 1.85–3.19).ConclusionOur study suggested that CTC+ was associated with a worse OS and PFS/DFS in the Asian population. The detection method, the threshold level of CTC+, therapeutic approaches, and sampling times would not affect its diagnostic and prognostic values.

BackgroundLate gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging has emerged as an important tool for assessment of patients with dilated cardiomyopathy (DCM). Electrocardiography (ECG) is an accessible, reproducible, low-cost diagnostic and prognostic tool. This study aimed to investigate the ECG characteristics associated with LGE, as well as to assess the prognostic significance of ECG in patients with DCM.MethodsConsecutive patients diagnosed with DCM by CMR [left ventricular ejection fraction (LVEF)

BackgroundPerturbation of osmolality is associated with increased mortality in adults and children in critically ill conditions. However, it is still unclear whether osmolality imbalance impacts the prognosis of critically ill infants. This study aimed to investigate the relationship between plasma osmolality and prognosis in critically ill infants within 24 h of admission.MethodsThis retrospective study enrolled 1,042 infants who had plasma osmolality data from 2010 to 2018. The initial plasma osmolality (within 24 h after admission) was extracted from the pediatric intensive care database (PIC V1.1). The locally weighted scatter-plot smoothing (LOWESS) and restricted cubic splines (RCS) methods were used to explore the approximate relationship between plasma osmolality and in-hospital mortality. Univariate and multivariate logistic regression analyses were used to further analyse this relationship. Kaplan–Meier analysis was applied to estimate the probability of hospital mortality within 90 days of admission. Subgroup analysis was employed to assess the impact of potential confounders (including postnatal days, gender, and gestational age).ResultsAn approximately“U”-shaped relationship between plasma osmolality and mortality was detected. In the logistic regression model, plasma osmolality 300 mmol/L (high osmolality group) was also significantly associated with mortality (P

Background: Treatment options for patients with triple-negative breast cancer (TNBC) remain limited to mainstay therapies owing to a lack of efficacious therapeutic targets. Accordingly, there is an urgent need to discover and identify novel molecular targets for the treatment and diagnosis of this disease. In this study, we analyzed the correlation of telomerase reverse transcriptase (TERT) methylation status with TERT expression, prognosis, and immune infiltration in TNBC and identified the role of TERT methylation in the regulation TNBC prognosis and immunotherapy. Methods: Data relating to the transcriptome, clinicopathological characteristics and methylation of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) database. TERT expression levels and differential methylation sites (DMSs) were detected. The correlations between TERT expression and DMSs were calculated. Kaplan–Meier curves was plotted to analyze the relationship between the survival of TNBC patients and the DMSs. The correlations of DMSs and TERT expression with several immunological characteristics of immune microenvironment (immune cell infiltration, immunomodulators, immune-related biological pathways, and immune checkpoints) were assessed. The results were validated using 40 TNBC patients from Sun Yat-sen University Cancer Center (SYSUCC). Results: Six DMSs were identified. Among them, four sites (cg11625005, cg07380026, cg17166338, and cg26006951) were within the TERT promoter, in which two sites (cg07380026 and cg26006951) were significantly related to the prognosis of patients with TNBC. Further validation using 40 TNBC samples from SYSUCC showed that the high methylation of the cg26006951 CpG site was associated with poor survival prognosis (P=0.0022). TERT expression was significantly correlated with pathological N stage and clinical stage, and cg07380026 were significantly associated with pathological T and N stages in the TCGA cohort. Moreover, the methylation site cg26006951, cg07380026 and TERT expression were significantly correlated with immune cell infiltration, common immunomodulators, and the level of the immune checkpoint receptor lymphocyte activation gene 3 (LAG-3) in TNBC patients. Conclusion: TERT promotertypermethylation plays an important role in TERT expression regulation and tumor microenvironment in TNBC. It is associated with overall survival and LAG-3 expression. TERT promoter hypermethylation may be a potential molecular biomarker for predicting response to the TERT inhibitors and immune checkpoint inhibitors in TNBC. [ABSTRACT FROM AUTHOR]

Uterus corpus endometrial cancer (UCEC) is associated with a high mortality rate. In this study, we examined the impact of long intergenic non-protein coding RNA 01234 (LINC01234) in the diagnosis and survival of UCEC using an open high-throughput sequencing database. The association between LINC01234 expression and UCEC clinical features was determined using the Wilcoxon rank sum test, logistic regression and Cox regression. To assess the classification effectiveness of LINC01234 in UCEC, the area under the receiver operating characteristic (ROC) curve (AUC) was performed. Then, Kaplan-Meier analysis was performed to determine the prognostic significance of LINC01234 in UCEC. The underlying regulatory mechanisms of LIN01234 were assessed using the Gene set enrichment analysis (GSEA), and the influence on immune infiltration cells was tested by the Spearman correlation method. Datebases showed LINC01234 was up-regulated in UCEC and associated with poor clinicopathologic characteristics. What's more quantitative real time polymerase chain reaction (qRTPCR) analyse of clinical tissue specimens, LINC01234 was actually high expression in UCEC. The results showed an AUC of 0.726, indicating that LINC01234 had a significant diagnostic value. Further, Kaplan-Meier analysis showed that high LINC01234 expression was associated with poorer progress free interval (PFI) (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.18-2.39, p = 0.004), diseasespecific survival (DSS) (HR: 2.17, 95% CI: 1.29-3.67, p = 0.004), overall survival (OS) (HR: 1.81, 95% CI: 1.19-2.75, p = 0.005). Cox regression analysis showed LINC01234 expression was an independent factor for DSS. Pathway enrichment and immune infiltration analysis showed the most likely mechanisms that LINC01234 promoted tumor progression. LINC01234 demonstrated diagnostic and prognostic potential in UCEC and was shown to exert its effects via various mechanisms, including cell proliferation, spermatogenesis, angiogenesis and immune response in the tumor microenvironment, to promote tumor progression; thus, indicating that it could be a target for treating UCEC. [ABSTRACT FROM AUTHOR]

Wilms tumor gene 1 (WT-1 gene) is overexpressed in most patients with acute myeloid leukemia (AML) and is an indicator for minimal residual disease (MRD) monitoring, but because the WT-1 gene has relatively low specificity, further studies of the prognostic value of a combination of the WT-1 and other genes are needed. The aim of this study was to explore the prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in AML. In AML, the transcript expression of the WT-1 gene was closely related to leukemic tumor burden and acted as an accurate molecular indicator for MRD detection. Most patients with low expression levels of the WT-1 gene after induction and consolidation therapy were significantly associated with favorable relapse-free survival (RFS) and overall survival (OS), but 17.6% of patients relapsed and died of primary disease. However, when analyzing the WT-1 gene combined with recurrent cytogenetic genes, none of the patients with low expression levels of the WT-1 gene and recurrent cytogenetic genes negative relapsed and died in the median follow-up time of 19 months (range: 3–94 months). Thus, the combination of the WT-1 gene and recurrent cytogenetic genes is a more accurate indicator for MRD monitoring and prognosis evaluation in AML patients. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors currently serve an important role in prolonging patients' overall survival. However, the prognostic signatures of immune checkpoint inhibitors in colorectal cancer (CRC) remain uncertain and more knowledge on the genetic characteristics of colorectal cancer is needed. Patients with CRC from The Cancer Genome Atlas were classified into high-immunity group and low-immunity group based on median scores from single-sample gene set enrichment analysis using the GSVA package. We explored immune status by immune scores, stromal scores and tumor purity scores in ESTIMATE package and surveyed the difference of immune cells distribution with CIBERSORT package. Eighteen genes were selected using the LASSO Cox regression method and a prognostic risk model was constructed. Compared with patients in the low-risk group, those in the high-risk group had a significantly shorter survival time. For assessment of the prognostic validity of the risk model, receiver operating characteristic curves with areas under the curve of 0.769, 0.774 and 0.771 for 1, 3 and 5 years respectively. Differences in molecular mechanisms between high- and low-risk groups were analyzed using the clusterProfiler package. Tumor Immune Dysfunction and Exclusion data were downloaded and analyzed. The top 5 enriched pathways in the high-risk group involved 'calcium signaling', 'dilated cardiomyopathy', 'extracellular matrix receptor interaction', 'hypertrophic cardiomyopathy' and 'neuroactive ligand receptor interaction'. HAMP was identified as a hub gene, which was highly expressed in tumor samples. The results of the present study indicate that the prognostic model based on both immune-related genes and HAMP has the potential to support personalized treatment. [ABSTRACT FROM AUTHOR]

The protein kinesin family member 26B (KIF26B) is aberrantly expressed in various cancers. However, its particular role and association with tumor immune infiltration in colon adenocarcinoma (COAD) remain unclear. All original data were downloaded directly from The Cancer Genome Atlas (TCGA), UCSC Xena, and Gene Expression Omnibus (GEO) databases and processed with R 3.6.3. KIF26B expression was analyzed using Oncomine, TIMER, TCGA, GEO databases, and our clinical specimens. KIF26B expression at the protein level was explored with Human Protein Atlas (HPA) database. The upstream miRNAs and lncRNAs were predicted by StarBase and validated using RT-qPCR. Correlation of KIF26B expression with the expression of immune-related or immune checkpoint genes and GSEA analysis of KIF26B-related genes were investigated via R software. Relationship of KIF26B expression with immune biomarkers or tumor immune infiltration levels was studied through GEPIA2 and TIMER databases. KIF26B was upregulated, and its overexpression was closely related to overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), T stage, N stage, and CEA levels in COAD. MIR4435-2HG/hsa-miR−500a−3p/KIF26B axis was identified as the promising regulatory pathway of KIF26B. KIF26B expression was positively correlated with immune-related genes, tumor immune infiltration, and biomarker genes of immune cells in COAD, and KIF26B-related genes were significantly enriched in macrophage activation-related pathways. Expression of immune checkpoint genes, including PDCD1, CD274, and CTLA4, was also closely related to KIF26B expression. Our results clarified that ncRNA-based increased KIF26B expression was associated with a worse prognosis and high tumor immune infiltration in COAD. [ABSTRACT FROM AUTHOR]

Objectives: To investigate thresholds for lymph node yield (LNY), lymph node density (LND), and pN in patients with oral squamous cell carcinoma in relation to previous findings in the literature. Study Design: Retrospective register‐based study. Setting: Copenhagen Oral Cavity Squamous Cell Carcinoma database. Methods: Appropriate thresholds for LNY, LND, and pN were determined by areas under the curve and subsequently subjected to multivariate analysis. Five‐year overall survival and 3‐year recurrence‐free survival were determined by Kaplan‐Meier survival curves. Results: In total, 413 patients diagnosed with oral squamous cell carcinoma were included. In the pN0 cohort, no superior/prognostic LNY cutoff values were detected. In the pN+ cohort, areas under the curve determined thresholds of LNY, LND, and pN to be 21 nodes, 5%, and 3 metastases, respectively. The 5‐year overall survival was 52% for patients with LNY ≥21 vs 38% for patients with LNY <21 (hazard ratio [HR], 1.49; 95% CI, 1.05‐2.11; P <.05), 60% for patients with LND ≤5% vs 38% for patients with LND >6% (HR, 1.63; 95% CI, 1.03‐2.57; P <.05), and 43% for patients with pN <3 vs 26% for patients with pN ≥3 (HR, 1.40; 95% CI, 1.04‐2.15; P <.05). Conclusions: Increased nodal yield, decreased LND, and decreasing number of pN were associated with significantly improved survival outcomes. LNY might serve as a prognosticator of survival as well as a surgical quality indicator. LND may have implications as a tool in cancer staging and treatment planning. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is an invariably fatal neurodegenerative disease with limited therapeutic options. There is an urgent need for novel biomarkers to be used as surrogates for new therapeutic trials and disease monitoring. In this study, we sought to systematically study creatine kinase isoenzyme MB (CK-MB) in a real-world cohort of ALS patients, assess the diagnostic performance, and evaluate its association with other laboratory and clinical parameters. We reviewed data from 194 consecutive patients that included 130 ALS patients and 64 disease control patients (primary lateral sclerosis [PLS], benign fasciculations syndrome [BFS], Huntington's disease [HD] and Alzheimer's disease [AD]). CK-MB was elevated in the sera of more than half of all patients with ALS. In patients with spinal-onset ALS, CK-MB levels were significantly higher than in patients with other neurodegenerative diseases. Patients with slower rates of functional decline had a significantly higher baseline CK-MB. Furthermore, CK-MB elevations correlated with cardiac troponin T (cTnT) and with revised ALS Functional Rating Scale (ALSFRS-R) bulbar subcategory. We posit that measuring CK-MB in ALS patients in a complimentary fashion could potentially aid in the diagnostic workup of ALS and help discriminate the disease from some ALS mimics and other neurodegenerative diseases. CK-MB levels also may provide valuable prognostic information regarding disease aggressiveness as well as correlations with specific phenotypic presentations. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UVM) is the most common primary ocular malignancy in adults and involves several types of regulated cell death. Cuproptosis is a novel method of regulating cell death by binding lipoylated TCA cycle proteins. There is still no research on the relationship between cuproptosis-related genes (CRGs) and UVM. Here, we aimed to develop a prognostic CRG signature for UVM. After a prognostic CRG signature was constructed, we determined the relationship between the signature and immune infiltration, bioinformatics analysis and experimental validation. Finally, a prognostic cuproptosis-related three-gene (CRTG) signature was constructed, which comprised ORAI2, ACADSB and SLC47A1. The risk score of the CRTG signature was negatively correlated with the overall survival (OS) and progression-free survival (PFS) of patients, which revealed strong predictive ability and its independent prognostic value. In addition, we found that the risk score was negative for chromosomes 3 and 6p, and positive for 8q, and high-risk UVM patients showed an increase in protumor immune infiltrates and a high expression of immune checkpoints. Finally, experimental validation verified that the migratory ability of MUM-2B cells was suppressed by the knockdown of the identified genes in vitro. We constructed a CRTG signature that is helpful in predicting prognosis and guiding treatment for patients with UVM. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Esophageal cancer (EC) is a highly malignant digestive system tumor that often lacks evident early symptoms and has a poor prognosis. Pyroptosis, a form of programmed cell death, has been shown to be associated with the occurrence and progression of many malignancies. However, its role in esophageal cancer remains unclear. This work aimed to evaluate the prognostic value of pyroptosis-related genes (PRGs) in EC using data from The Cancer Genome Atlas (TCGA) cohort. MATERIALS AND METHODS: The RNA-seq data from 171 esophageal samples in the TCGA database were employed. Differential expression genes (DEGs) between tumor and non-tumor samples were compared. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analyses were performed using the “clusterProfiler” package in R. Furthermore, based on the DEGs, all esophageal cancer cases were classified into three subtypes. A risk model for gene features was established using the LASSO regression method, and EC patients in the TCGA cohort were divided into high-risk and low-risk groups. RESULTS: A total of 614 PRGs were identified. Among them, 32 DEGs (31 upregulated and 1 downregulated) were found between normal esophageal tissue and EC tissue. PPI analysis identified key genes including IL-1β, CASP1, AIM2, HMGB1, GSDMD, PYCARD, IL-18, BAK1, and TP53. On the other hand, the low-risk group exhibited a significantly higher survival rate than the high-risk group (p < 0.001). Combined with the clinical characteristics of the TCGA cohort, it was found that the risk score was an independent prognostic factor for overall survival (OS) prediction in EC patients. KEGG and GO analyses revealed the enrichment of genes associated with cell proliferation in the high-risk group. CONCLUSIONS: PRGs play a crucial role in the occurrence and development of EC and can be used to predict the prognosis of EC patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to perform a retrospective analysis of patients with acute anterior wall ST-segment elevation myocardial infarction (AAW-STEMI) whose left anterior descending (LAD) artery was completely occluded and reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influencing factors and prognostic value of left ventricular systolic dysfunction (LVSD) in the acute phase of acute myocardial infarction (AMI). Methods: A total of 304 patients with AAW-STEMI were selected. The selected patients were divided into two groups: the preserved left ventricular ejection fraction (pLVEF) group (LVEF ≥ 50%, n = 185) and the reduced left ventricular ejection fraction (rLVEF) group (LVEF < 50%, n = 119). The influencing factors of LVSD and their predictive value for LVSD were analyzed. Patients were followed up by examining outpatient records and via telephone. The predictive value of LVSD for the cardiovascular mortality of patients with AAW-STEMI was analyzed. Results: Age, heart rate (HR) at admission, number of ST-segment elevation leads (STELs), peak creatine kinase (CK) and symptom to wire-crossing (STW) time were independent risk factors for LVSD (P < 0.05). The receiver operating characteristic (ROC) analysis showed that the peak CK had the strongest predictive value for LVSD, with an area under the curve (AUC) of 0.742 (CI, 0.687 to 0.797) as the outcome. At a median follow-up of 47 months (interquartile range, 27 to 64 months), the Kaplan‒Meier survival curves up to 6-year follow-up revealed a total of 8 patients succumbed to cardiovascular disease, with 7 (6.54%) in the rLVEF group and 1 (0.56%) in the pLVEF group, respectively (hazard ratio: 12.11, [P = 0.02]). Univariate and multivariate Cox proportional hazards regression analysis demonstrated that rLVEF was an independent risk predictor of cardiovascular death in patients with AAW-STEMI discharged after PPCI (P < 0.01). Conclusions: Age, HR at admission, number of STELs, peak CK, and STW time may be used to identify patients with a high risk of heart failure (HF) in a timely manner and initiate early standard therapy for incident LVSD in the acute phase of AAW-STEMI reperfused by PPCI. A trend toward increased cardiovascular mortality at follow-up was significantly linked to LVSD. [ABSTRACT FROM AUTHOR]

Background and aims: Preclinical data suggest that activation of the adaptive immune system is critical for myocardial repair processes in acute myocardial infarction. The aim of the present study was to determine the clinical value of baseline effector T cell chemokine IP-10 blood levels in the acute phase of STsegment elevation myocardial infarction (STEMI) for the prediction of the left ventricular function changes and cardiovascular outcomes after STEMI. Methods: Serum IP-10 levels were retrospectively quantified in two independent cohorts of STEMI patients undergoing primary percutaneous coronary intervention. Results: We report a biphasic response of the effector T cell trafficking chemokine IP-10 characterized by an initial increase of its serum levels in the acute phase of STEMI followed by a rapid reduction at 90min post reperfusion. Patients at the highest IP-10 tertile presented also with more CD4 effector memory T cells (CD4 TEM cells), but not other T cell subtypes, in blood. In the Newcastle cohort (n=47), patients in the highest IP-10 tertile or CD4 TEM cells at admission exhibited an improved cardiac systolic function 12 weeks after STEMI compared to patients in the lowest IP-10 tertile. In the Heidelberg cohort (n=331), STEMI patients were followed for a median of 540 days for major adverse cardiovascular events (MACE). Patients presenting with higher serum IP-10 levels at admission had a lower risk for MACE after adjustment for traditional risk factors, CRP and high-sensitivity troponin-T levels (highest vs. rest quarters: HR [95% CI]=0.420 [0.218-0.808]). Conclusion: Increased serum levels of IP-10 in the acute phase of STEMI predict a better recovery in cardiac systolic function and less adverse events in patients after STEMI. [ABSTRACT FROM AUTHOR]

Iron metabolism-related genes (IMRGs) play important roles in the prognostic assessment of many tumours. However, IMRGs have not been reported as prognostic biomarkers in bladder urothelial carcinoma (BLCA). Gene expression profiles and clinical data from BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. We used the DESeq2 package to screen for differentially expressed genes (DEGs). The predictive values of the differentially expressed IMRGs in BLCA patients were further evaluated using univariate Cox regression analysis. The risk-scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm. The performance of this model for predicting the prognosis of BLCA patients in TCGA-BLCA cohort was assessed using Kaplan–Meier (K–M) and receiver operating characteristic (ROC) curves. This risk-scoring model was combined with the clinicopathological characteristics of BLCA patients in a multiple regression analysis, and a nomogram was constructed using the independent predictors identified. ROC analysis and calibration curves were adapted to test the predictive ability of the nomogram. Gene set enrichment analysis (GSEA) was used to identify potential molecular pathways and processes enriched by differential expression genes between risk groups. Finally, we explored the ability of the risk-scoring model to assess immune cell infiltration levels through a correlation analysis. Fourteen identified IMRGs with prognostic value were incorporated into the risk-scoring model. The ROC and K–M survival curves indicated that the model could effectively predict the overall survival (OS) outcomes of BLCA patients. The multiple regression analysis revealed that the risk-scoring model could be used as an independent prognostic factor for BLCA patients, and the associated nomogram could effectively predict the OS outcomes of BLCA patients. GSEA revealed that the DEGs between the risk groups were mainly involved in biological processes such as developmental process, cell cycle, mitosis, RHO GTPase reaction, DNA repair, and extracellular matrix regulation. The immune infiltration analysis showed that the infiltration levels of immune cells such as natural killer cells, memory T cells, effector T cells, Th2 cells, and macrophages differed significantly between the risk groups. IMRGs screening revealed prognosis-associated genes. The prognostic model constructed could effectively predict the prognosis of BLCA patients, and the identified genes represent potential targets for BLCA treatment. [ABSTRACT FROM AUTHOR]

Purpose: Dishevelled-associated activator of morphogenesis 2 (DAAM2) is a formin protein and has a potential role in the tumor metastasis. The prognostic value of DAAM2 in pan-cancer is investigated in this study. Methods: TCGA and GTEx database were downloaded to perform bioinformatics analysis and ROC curves. Then we explored protein–protein interaction and GO-KEGG enrichment to figure out the protein pathways associated with DAAM2 and studied DAAM2-related immune infiltration and methylation. Fifteen pairs of BRCA clinical samples were enrolled to determine the expression and distribution of DAAM2 in BRCA sections by immunohistochemistry. Finally, BRCA cells were transfected with siRNA targeting DAAM2 and subsequently subject to cell proliferation, migration, and invasion assays. Results: DAAM2 was closely related to the diagnosis and clinical characteristics of lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and breast cancer (BRCA). Survival curve analysis demonstrated DAAM2 served as a potential prognostic indicator of LGG and LIHC (P = 0.0029 and P = 0.025, respectively). DAAM2 was mainly participated in signaling pathways mediating cytoskeleton regulation and tumor development. The correlation of DAAM2 with tumor-infiltrating immune cells (TIICs) and methylation levels was conducive to the prediction of novel biomarkers of pan-carcinoma. DAAM2 was highly expressed in BRCA tissues than that in paracancerous tissues. The proliferation, invasion, and migration of BRCA cells were inhibited by DAAM2 siRNA. Conclusion: DAAM2 had a specific value in foretelling the prognosis of LGG, LIHC, and BRCA. High expression level of DAAM2 has longer survival rates in LGG and LIHC. The knockdown of DAAM2 retards the proliferation, invasion, and migration of BRCA cells. This study provides a novel sight of DAAM2 into the exploration of a potential biomarker in pan-cancer. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is among the deadliest diseases with countless incidences and deaths each year. Helicobacter pylori (Hp) is the primary type of microbe that colonizes the stomach. In recent years, increasing evidence has demonstrated that Hp infection is one of the main risk factors for GC. Elucidating the molecular mechanism of how Hp leads to GC will not only benefit the treatment of GC, but also boost the development of therapeutics for other gastric disorders caused by Hp infection. In this study, we aimed to identify innate immunity-related genes in GC and investigate their potentials as prognostic markers and therapeutic targets for Hp-related GC. Methods: Firstly, we analyzed the differentially expressed innate immunity-related genes in GC samples from the TCGA database. Then prognostic correlation analysis was carried out to explore the prognostic value of these candidate genes. By combing transcriptome data, somatic mutation data, and clinical data, co-expression analysis, functional enrichment analysis, tumor mutational burden analysis, and immune infiltration analysis were performed to reveal the pathological relevance of the candidate gene. Finally, ceRNA network was constructed to identify the genes and pathways for the regulation of the candidate gene. Results: We revealed that protein tyrosine phosphatase non-receptor type 20 (PTPN20) is a significant prognostic marker in Hp-related GC. Thus, PTPN20 levels have the potential to efficiently predict the survival of Hp-related GC patients. In addition, PTPN20 is associated with immune cell infiltration and tumor mutation burden in these GC patients. Moreover, we have also identified PTPN20-related genes, PTPN20 protein-protein interactions, and the PTPN20 ceRNA network. Conclusion: Our data suggest that PTPN20 may have critical functions in Hp-related GC. Targeting PTPN20 may be a promising way to treat Hp-related GC. [ABSTRACT FROM AUTHOR]

Background: Whether isocitrate dehydrogenase 2 (IDH2) R140 and R172 gene mutations affect the prognosis of patients with acute myeloid leukemia (AML) is controversial. Here, we performed a meta-analysis to assess their prognostic value. Methods: Eligible studies were systematically searched from PubMed, Embase, the Cochrane Library and Chinese databases up to June 1, 2022. We extracted the hazard ratios (HRs) and their 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) to carry out a meta-analysis by a fixed effect model or random effect model according to the heterogeneity between studies. Results: A total of 12725 AML patients from 11 studies were included in this meta-analysis, of which 1111 (8.7%) and 305 (2.4%) had IDH2R140 and IDH2R172 mutations, respectively. The results revealed that both IDH2R140 and IDH2R172 mutations had no significant effect on OS (IDH2R140: HR = 0.92, 95% CI: 0.77–1.10, P = 0.365; IDH2R172: HR = 0.91, 95% CI: 0.65–1.28, P = 0.590) or PFS (IDH2R140: HR = 1.02, 95% CI: 0.75–1.40, P = 0.881; IDH2R172: HR = 1.31, 95% CI: 0.78–2.22, P = 0.306) in AML patients. Subgroup analysis of AML patients with IDH2R140 mutation revealed that studies from the USA (HR = 0.60, 95% CI: 0.41–0.89, P = 0.010) and ≤ 50 years old (HR = 0.63, 95% CI: 0.50–0.80, P = 0.000) had longer OS. However, studies from Sweden (HR = 1.94, 95% CI: 1.07–3.53, P = 0.030) had shorter OS. Meanwhile, subgroup analysis of AML patients with IDH2R172 mutation showed that studies from Germany/Austria (HR = 0.76, 95% CI: 0.61–0.94, P = 0.012) and from Sweden (HR = 0.22, 95% CI: 0.07–0.74, P = 0.014) had longer OS, whereas studies from the UK (HR = 1.49, 95% CI: 1.13–1.96, P = 0.005) and studies with nonmultivariate analysis of data type (HR = 1.35, 95% CI: 1.06–1.73, P = 0.014) had shorter OS. In addition, our study also found that patients with IDH2R140 mutation had significantly longer OS (HR = 0.61, 95% CI: 0.39–0.96, P = 0.032) and PFS (HR = 0.31, 95% CI: 0.18–0.52, P = 0.021) than patients with IDH2R172 mutation, despite some degree of heterogeneity. Conclusions: This meta-analysis demonstrates that IDH2R140 mutation improves OS in younger AML patients and that the prognostic value of IDH2R172 mutation is significantly heterogeneous. Differences in region and data type have a significant impact on the prognosis of AML patients with IDH2R140 and/or IDH2R172 mutations. Additionally, AML patients with IDH2R140 mutation have a better prognosis than those with IDH2R172 mutations, albeit with some degree of heterogeneity. [ABSTRACT FROM AUTHOR]

Purpose: Cuproptosis-related long non-coding RNA (lncRNA) diseases are associated with the occurrence and development of tumors. This study aimed to investigate whether cuproptosis-related lncRNA can predict the prognosis of patients with lung adenocarcinoma (LUAD). Methods: Cuproptosis-related lncRNA prognosis (CLPS) model was successfully constructed through cox regression and lasso regression analyses. Then, the prognostic value of CLPS model was tested through the survival analysis, the ROC curve and the nomogram. Finally, the correlation of CLPS model with tumor immunity and tumor mutation burden was analyzed, and the potential susceptibility of drugs for LUAD were predicted. Results: CLPS model for LUAD (AC090948.1, CRIM1-DT, AC026356.2, AC004832.5, AL161431.1) was successfully constructed, which has an independent prognostic value. Furthermore, the risk score of CLPS model was correlated with tumor immune characteristics and immune escape, which can predict the sensitivity of drugs including Cisplatin, Etoposide, Gemcitabine, and Erlotinib. Conclusions: In conclusion, it was found that CLPS model was associated with tumor immunity and tumor mutation load, which also predicted four potentially sensitive drugs for LUAD patients at different risks. [ABSTRACT FROM AUTHOR]

Abstract Background DNA replication alteration is a hallmark of patients with lung adenocarcinoma (LUAD) and is frequently observed in LUAD progression. Origin recognition complex (ORC) 1, ORC2, ORC3, ORC4, ORC5, and ORC6 form a replication–initiator complex to mediate DNA replication, which plays a key role in carcinogenesis, while their roles in LUAD remain poorly understood. Methods The mRNA and protein expression of ORCs was confirmed by the GEPIA, HPA, CPTAC, and TCGA databases. The protein–protein interaction network was analyzed by the GeneMANIA database. Functional enrichment was confirmed by the Metascape database. The effects of ORCs on immune infiltration were validated by the TIMER database. The prognostic significance of ORCs in LUAD was confirmed by the KM‐plot and GENT2 databases. DNA alteration and protein structure were determined in the cBioProtal and PDB databases. Moreover, the protein expression and prognostic value of ORCs were confirmed in our LUAD data sets by immunohistochemistry (IHC) staining. Results ORC mRNA and protein were significantly increased in patients with LUAD compared with corresponding normal tissue samples. The results of IHC staining analysis were similar result to those of the above bioinformatics analysis. Furthermore, ORC1 and ORC6 had significant prognostic values for LUAD patients. Furthermore, the ORC cooperatively promoted LUAD development by driving DNA replication, cellular senescence, and metabolic processes. Conclusion The ORC, especially ORC1/6, has important prognostic and expression significance for LUAD patients.

Abstract Background Heart failure- (HF) and arrhythmia-related complications are the main causes of morbidity and mortality in patients with nonischemic dilated cardiomyopathy (NIDCM). Cardiovascular magnetic resonance (CMR) imaging is a noninvasive tool for risk stratification based on fibrosis assessment. Diffuse interstitial fibrosis in NIDCM may be a limitation for fibrosis assessment through late gadolinium enhancement (LGE), which might be overcome through quantitative T1 and extracellular volume (ECV) assessment. T1 and ECV prognostic value for arrhythmia-related events remain poorly investigated. We asked whether T1 and ECV have a prognostic value in NIDCM patients. Methods This prospective multicenter study analyzed 225 patients with NIDCM confirmed by CMR who were followed up for 2 years. CMR evaluation included LGE, native T1 mapping and ECV values. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE) which was divided in two groups: HF-related events and arrhythmia-related events. Optimal cutoffs for prediction of MACE occurrence were calculated for all CMR quantitative values. Results Fifty-eight patients (26%) developed a MACE during follow-up, 42 patients (19%) with HF-related events and 16 patients (7%) arrhythmia-related events. T1 Z-score (p = 0.008) and global ECV (p = 0.001) were associated with HF-related events occurrence, in addition to left ventricular ejection fraction (p 32.1% (optimal cutoff) remained the only CMR independent predictor of HF-related events occurrence (HR 2.15 [1.14–4.07], p = 0.018). In the arrhythmia-related events group, patients had increased native T1 Z-score and ECV values, with both T1 Z-score > 4.2 and ECV > 30.5% (optimal cutoffs) being independent predictors of arrhythmia-related events occurrence (respectively, HR 2.86 [1.06–7.68], p = 0.037 and HR 2.72 [1.01–7.36], p = 0.049). Conclusions ECV was the sole independent predictive factor for both HF- and arrhythmia-related events in NIDCM patients. Native T1 was also an independent predictor in arrhythmia-related events occurrence. The addition of ECV and more importantly native T1 in the decision-making algorithm may improve arrhythmia risk stratification in NIDCM patients. Trial registration NCT02352129. Registered 2nd February 2015—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02352129

Abstract Background Recent reports suggested that circulating exosomal microRNAs (exomiRs) may serve as non-invasive prediction biomarkers in gastrointestinal (GI) cancers, yet their clinicopathological and prognostic values need to be more clarified. Hence, the present meta-analysis was aimed to quantitatively assess the evidence regarding the association between circulating exomiRs and prognosis in GI cancer patients. Methods A comprehensive search was carried out in prominent literature databases, including PubMed, ISI Web of Science, Scopus, and Embase. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were gathered to evaluate the strength of the association. The quality assessment was investigated through the Newcastle-Ottawa Scale (NOS) and publication bias via Eggers’ test and funnel plots. Results A total of 47 studies, comprising of 4881 patients, were considered eligible for this meta-analysis. Both up-regulated and down-regulated circulating exomiRs are significantly associated with differentiation (HR = 1.353, P = 0.015; HR = 1.504, P = 0.016), TNM stage (HR = 2.058, P

Abstract Background Many cytogenetic changes and gene mutations are associated with acute myeloid leukemia (AML) survival outcomes. CD56 is related to poor prognosis when expressed in adult AML patients. However, the prognostic value of CD56 in children with AML has rarely been reported. In this research, we aimed to evaluate the prognostic value of CD56 in childhood AML. Methods The present retrospective study included 145 newly diagnosed pediatric patients with de novo AML (excluding AML-M3) in two hospitals between January 2015 and April 2021. Results The total median (range) age was 75 (8–176) months, and the median follow-up time was 35 months. No significant difference in the 3-year overall survival rate was noted between the CD56-positive and CD56-negative groups (67.0% vs. 79.3%, P = 0.157) who received chemotherapy. However, among high-risk patients, the CD56-positive group had a worse overall survival rate and event-free survival rate (P

Abstract Background Patients with lower-limb osteomyelitis (LLOM) may experience major adverse events, such as lower-leg amputations or death; therefore, early diagnosis and risk stratification are essential to improve outcomes. Ga-scintigraphy is commonly used for diagnosing inflammatory diseases. Although the diagnostic performance of planar and SPECT imaging for localized lesions is limited, SPECT/CT, which simultaneously acquires functional and anatomical definition, has resulted in significant improvements to diagnostic confidence. While quantitative Ga-SPECT/CT is an emerging approach to improve diagnoses, its diagnostic performance has not been sufficiently evaluated to date. Therefore, this study aimed to evaluate the diagnostic performance of Ga-SPECT/CT with quantitative analyses for patients with LLOM. Methods A total of 103 consecutive patients suspected of LLOM between April 2012 and October 2016 were analyzed. All patients underwent Ga-scintigraphy with SPECT/CT imaging. Findings were assessed visually, with higher than background accumulation considered positive, and quantitatively, using Ga-SPECT/CT images to calculate the lesion-to-background ratio (LBR), the maximum standardized uptake value (SUVmax), and total lesion uptake (TLU). Diagnoses were confirmed using pathological examinations and patient outcomes, and diagnostic performances of planar, SPECT, and SPECT/CT images were compared. To evaluate prognostic performance, all patients were observed for 5 years for occurrences of major adverse events (MAE), defined as recurrence of osteomyelitis, major leg amputation, or fatal event. Multivariate Cox regression was performed to evaluate outcome factors. Results The overall diagnoses indicated that 54 out of 103 patients had LLOM. LBR, SUVmax, and TLU were significantly higher in patients with LLOM (12.23 vs. 1.00, 4.85 vs. 1.34, and 68.77 vs. 8.63, respectively; p

Background: Hyperglycemia detected during acute illness-like ischemic stroke is associated with adverse outcomes more than in normoglycemic patients. However,very limited data regarding stress hyperglycemia and its prognostic value are available for our Indian population. Aims and Objectives: This study was aimed at comparing the stress hyperglycemic and normoglycemic patients in terms of mortality and functional recovery during 28 days follow-up assessed by the Barthel index for Activities of Daily Living. Materials and Methods: Adult non-diabetic patients with ischemic stroke were assessed for random venous blood glucose and HbA1c levels and divided into two groups: Patients with hyperglycemia and normoglycemia. The Barthel Index for Activities of Daily Living was used to compare mortality and functional recovery on the day of admission, day 3, and day 28 after stroke. Results: Mortality over the 28 days follow-up was significantly higher in hyperglycemic patients (45% vs. 20%,P=0.02). The Barthel Index score on admission (day 0) was 8.75±7.41 among stress hyperglycemic patient whereas it was13.54±11.12 among normoglycemic patient, which was significantly different (P=0.028). Similarly, day 3 (18.89±6.08 vs. 23.26±13.05, P

Abstract Background Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. N6-methyladenosine (m6A) modification has dual biological functions in RNA modification and plays an important role in HCC. Methods The GEO, TCGA, ONCOMINE, UALCAN, GEPIA, Kaplan–Meier plotter, cBioPortal for Cancer Genomics, STRING and TIMER2 databases were used for bioinformatic analyses. Quantitative polymerase chain reaction and western blotting were used to detect the expression of m6A regulators in HCC tissues. Results The transcription of m6A regulators was upregulated in patients with HCC, and overexpression of YTHDF1/2, YTHDC1, RBM15 and METTL3 was significantly correlated with clinical stages of HCC. In addition, downregulation of ZC3H13 and METTL14 and upregulation of other m6A regulators were associated with a poor prognosis. A high mutation rate (89%) of m6A regulators was also observed in patients with HCC, and mutations in methylation regulators were associated with poor overall survival and disease-free survival. Finally, the expression of the YTHDF family was significantly associated with immune infiltration in the HCC microenvironment. Conclusion m6A regulators and programmed death-ligand 1 may play an important role in the tumorigenesis and immune invasion and escape of HCC and may be risk factors affecting the survival of patients with HCC.

Abstract Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection. Hematoxylin and eosin staining was performed to investigate the presence, the abundance, the maturation, and the location of TLSs. We explored the cellular composition of TLSs using traditional immunohistochemistry in serial sections. The prognostic value of TLSs was investigated by univariate and multivariate analyses. A nomogram was constructed to predict the prognosis. TLS‐positive tumors were infiltrated with more CD45+ leukocytes, CD20+ B cells, CD4+ and CD8+ T cells, and CD11c+ dendritic cells（DCs） compared with negative tumors. Kaplan–Meier curves showed that the presence and the abundance of TLSs were associated with longer disease‐free survival (DFS) (p = 0.0130) and overall survival (OS) (p = 0.0164). In addition, patients with tumors containing more CD20+ B cell infiltration had longer DFS (p = 0.0105) and OS (p = 0.0341). Multivariate analyses demonstrated that the presence of TLSs was an independent prognostic factor for DFS (hazard ratio [HR] = 0.384, p

Ting Liang,1– 6 Ding Xiao,2,3,7 Shanshan Lu,2,3 Xu Ye,8 Zhiqiang Xiao1– 3 1National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 3Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 4Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 5Hunan Hematology Oncology Clinical Medical Research Center, Changsha, 410008, People’s Republic of China; 6National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 7Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 8Department of Radiation Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410008, People’s Republic of ChinaCorrespondence: Zhiqiang Xiao, National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, 410008, People’s Republic of China, Tel +86-13873146236, Email zqxiao2001@hotmail.comPurpose: To evaluate the prognostic value of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), and macrophage migration inhibitory factor (MIF) in non-metastatic nasopharyngeal carcinoma (NPC) patients undergoing radical radiotherapy.Patients and Methods: A serum panel compromising the inflammatory factors was analyzed in 372 NPC patients before and after radiotherapy. Independent prognostic factors were screened out using multivariate Cox regression analysis. A prediction model was built based on the training set data and validated using the test set data. The prognostic value of these factors was evaluated using the time-dependent receiver operating characteristic (ROC) curve and an integrated time-averaged area under the curve (AUC).Results: The baseline levels of IL-6, GM-CSF, and MIF were independent factors associated with poor OS and DMFS. A predictive model base established combining the baseline levels of these factors. The AUC values for the test set were 0.9828, 0.9968, and 0.9571 at 1, 3, and 5 years, respectively, compared to 0.9978, 0.9981, and 0.9222 for the training set, respectively. The AUC values for DMFS at 1, 3, and 5-years for the training set were 0.8744, 0.8951, and 0.9358, respectively, compared to 0.9525, 0.9663, and 0.9625 for the test set, respectively. The combination of post-treatment levels of IL-6, GM-CSF, and LIF also had good predictive value for OS with an AUC value > 0.85 during follow-up.Conclusion: IL-6, GM-CSF, and MIF baseline levels are powerful prognostic factors for non-metastatic NPC patients. The combination of these factors effectively predicts OS and DMFS in non-metastatic NPC patients.Keywords: nasopharyngeal carcinoma, inflammatory factor, radical radiotherapy, prognostic value, overall survival

Background: Previous studies have shown that systemic inflammation indicators could predict the survival outcomes of patients with malignant tumors receiving various treatments. Radiotherapy, as a crucial treatment modality, effectively alleviates discomfort in patients with bone metastasis (BM) and greatly improves the quality of life for them. This study aimed to investigate the prognostic value of systemic inflammation index in hepatocellular carcinoma (HCC) patients with BM treated with radiotherapy. Methods: We retrospectively analyzed clinical data collected from HCC patients with BM who received radiotherapy in our institution between January 2017 and December 2021. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were derived to determine their relationship with overall survival (OS) and progression-free survival (PFS), using the Kaplan-Meier survival curves. The optimal cut-off value of the systemic inflammation indicators for predicting prognosis was assessed by receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were performed to ultimately evaluate the factors associated with survival. Results: The study included 239 patients with a median 14-month follow-up. The median OS was 18 months (95% confidence interval [CI] = 12.0-24.0) and the median PFS was 8.5 months (95% CI = 6.5-9.5). The optimal cut-off values for the patients were determined by ROC curve analysis as follows: SII =395.05, NLR=5.43 and PLR = 108.23. The area under the receiver operating characteristic curve values for SII, NLR and PLR in disease control prediction were 0.750, 0.665 and 0.676, respectively. Elevated systemic immune-inflammation index (SII>395.05) and higher NLR (NLR>5.43) were independently associated with poor OS and PFS. In multivariate analysis, Child-Pugh class (P = 0.038), intrahepatic tumor controlled (P = 0.019), SII (P = 0.001) and NLR (P = 0.007) were independent prognostic factors of OS and Child-Pugh class (P = 0.042), SII (P < 0.001) and NLR (P = 0.002) were independently correlated with PFS. Conclusion: NLR and SII were associated with poor prognosis in HCC patients with BM receiving radiotherapy and might be considered reliable and independent prognostic biomarkers for HCC patients with BM. [ABSTRACT FROM AUTHOR]