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Background: Growing evidence has indicated that some inflammatory markers, including lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), can be used as indicators in the prognosis of colorectal cancer (CRC). However, there is controversy concerning what is the best predictor of prognosis in CRC., Methods: A cohort of 1744 CRC patients in our institution was analyzed retrospectively. Harrell's concordance index (c-index) and Bayesian information criterion (BIC) were used to determine the optimal cut-off values of inflammatory markers and compare their predictive capacity. The association of inflammatory markers with overall survival (OS) and cancer-specific survival (CSS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model., Results: The multivariate analysis indicated that among these inflammatory markers, NLR (< 2.0 vs. ≥ 2.0) was the only independent prognostic factor for poor OS [hazard ratio (HR) = 0.758, 95% confidence intervals (CI) = 0.598-0.960, P = 0.021)] and CSS (HR = 0.738, 95% CI = 0.573-0.950, P = 0.018). Among these inflammatory markers, the c-index and BIC value for NLR were maximum and minimum for OS, respectively. In addition, the c-index was higher and the BIC value was smaller in TNM staging combined with NLR compared with the values obtained in TNM staging alone., Conclusion: NLR is a superior indicator of prognosis compared with LMR, PLR, and PNI in CRC patients, and NLR may serve as an additional indicator based on the current tumor staging system.

Background: Recent studies have provided evidence supporting the functional role and mechanism of lactate in suppressing anticancer immunity. However, there is no systematic analysis of lactate metabolism-related genes (LMRGs) and ovarian cancer (OV) prognosis. Results: Six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) were selected as prognostic genes and a prognostic model was utilized. Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) analyses were further performed and indicated that the prognostic model was effective. Subsequently, the neoplasm_cancer_status and RiskScore were determined as independent prognostic factors, and a nomogram was established with relatively accurate forecasting ability. Additionally, 2 types of immune cells (Central memory CD8 T cell and Immature B cell), 4 types of immune functions (APC co inhibition, DCs, Tfh and Th1 cells), 9 immune checkpoints (BTLA, CTLA4, IDO1, LAG3, VTCN1, CXCL10, CXCL9, IFNG, CD27) and tumor immune dysfunction and exclusion (TIDE) scores were significantly different between risk groups. The expression of 6 genes were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the expression of 6 genes were higher in the high-grade serous carcinoma (HGSC) samples. Conclusion: A prognostic model related to lactate metabolism was established for OV based on six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) that could provide new insights into therapy. [ABSTRACT FROM AUTHOR]

Introduction: Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disease characterized by ocular albinism (OA) or oculocutaneous albinism (OCA), platelet dysfunction, and other symptoms. This study aimed to analyze the molecular defect in two Chinese families with suspected OA, as well as to investigate the profile of HPS6 variants and their genotype-phenotype correlations. Methods: Seven members from two families were recruited and underwent clinical ophthalmologic examinations. The genomic DNA was extracted from peripheral blood leukocytes. Whole-exome sequencing was performed on the proband of family JX. The single coding exon of HPS6 was directly Sanger sequenced based on PCR amplification in all available family members. An additional 46 probands from families or sporadic cases with the pathogenic variants of HPS6 reported in the literature were reviewed. Results: We identified two different compound heterozygous truncating variants of HPS6 in probands with suspected OA from two independent families. The proband of family JX had c.1674dup and c.503-504del variants, and the other proband from family CZ had a nonsense variant of c.1114C>T and a frameshift variant of c.1556del. Among them, c.1674dup and c.1556del variants in HPS6 have not been reported previously. Therefore, our patients were diagnosed as HPS6 disease by molecular diagnostics. In the retrospective cohort of HPS6 patients, we delineated the profile of HPS6 variants and revealed a significant overlap between CpG islands and the variants of HPS6, suggesting a potential link between DNA methylation and HPS6 variants. We also observed a spatial aggregation of the variants in 3D structure of HPS6 protein, implying the possible functional significance of these structural regions. In addition, we did not find any significant genotype-phenotype correlation of HPS6, and neither did we observe a correlation between the truncation length of the HPS6 protein and the phenotype of HPS6 disease. Conclusion: Our research expands the spectrum of HPS6 variants, providing a comprehensive delineation of their profile and systematically investigating genotype-phenotype correlations in HPS6. These findings could offer potentially valuable clues for investigating the molecular mechanism underlying HPS6 pathogenesis, as well as aiding the clinical diagnosis of HPS6 patients and improving disease prognosis. [ABSTRACT FROM AUTHOR]

Background: Hepatic resection is a potentially curative treatment for patients with hepatocellular carcinoma (HCC). The treatment of elderly patients with HCC has always been difficult. With the development of geriatrics and geriatric surgery, the number of elderly patients with HCC undergoing hepatectomy has gradually increased. To further improve the long-term prognosis of elderly patients with hepatocellular carcinoma undergoing surgery, it is necessary to study the related perioperative factors. Our aim was to study the impact of preoperative and intraoperative factors on the long-term survival of elderly patients with HCC who underwent hepatectomy. Methods: A total of 151 elderly patients with HCC who underwent hepatectomy were retrospectively studied. Univariate and multivariate Cox regression analyses were performed for preoperative- and intraoperative-related prognostic factors. Results: The 1-, 3-, 5- and 10-year overall survival rates of elderly patients with HCC who underwent resection were 79.5%, 60.8%, 46.6%, and 25.4%, respectively. Multivariate analyses identified four independent predictors of long-term prognosis: Child–Pugh grade (B/C versus A: HR[hazard ratio] = 2.318, P = 0.019), alpha-fetoprotein value (> 20 ng/ml versus ≤ 20 ng/ml: HR = 1.972, P = 0.005), resection style (anatomical versus no anatomical: HR = 1.976, P = 0.006), and intraoperative blood loss (> 400 ml versus ≤ 400 ml: HR = 2.008, P = 0.003). Conclusions: Poor survival of elderly patients with HCC who underwent hepatectomy was correlated with the preoperative and intraoperative factors of Child–Pugh grade, Alpha-fetoprotein value, resection style, and intraoperative blood loss. [ABSTRACT FROM AUTHOR]

Background: Immunoinflammatory and nutritional markers, such as the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and Onodera's prognostic nutritional index (OPNI), have gained considerable attention and have been preliminarily revealed as prognostic markers of gastrointestinal stromal tumors (GISTs). Methods: In this study, we first investigated the prognostic value of OPNI in GISTs treated with or without TKIs based on the propensity score matching (PSM) method. All of the patients had received surgical resection for primary GIST, and data from 2010 to 2018 were initially and retrospectively identified from our gastrointestinal center. Recurrence-free survival (RFS) was calculated by the Kaplan–Meier method and compared by the log-rank test. Results: The patients were divided into groups treated and not treated with TKIs, and we used the propensity score matching method to homogenize their baseline data. Multivariate Cox proportional hazard regression models were applied to identify associations with outcome variables. A total of 563 GISTs were initially chosen, and 280 of them were included for analysis under the inclusion criteria. After PSM, there were 200 patients included. Multivariate analyses identified OPNI as an independent prognostic marker that was associated with primary site, tumor size, mitotic index, tumor rupture, necrosis, and modified NIH risk classification. Low OPNI (< 42.6; HR 0.409; P < 0.001) was associated with worse RFS. Conclusions: Preoperative OPNI is a novel and useful prognostic marker for GISTs both treated and not treated with TKIs. Higher NLR and PLR have negative effects on RFS. [ABSTRACT FROM AUTHOR]

Background: Growing evidence has indicated that some inflammatory markers, including lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), can be used as indicators in the prognosis of colorectal cancer (CRC). However, there is controversy concerning what is the best predictor of prognosis in CRC.Methods: A cohort of 1744 CRC patients in our institution was analyzed retrospectively. Harrell's concordance index (c-index) and Bayesian information criterion (BIC) were used to determine the optimal cut-off values of inflammatory markers and compare their predictive capacity. The association of inflammatory markers with overall survival (OS) and cancer-specific survival (CSS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model.Results: The multivariate analysis indicated that among these inflammatory markers, NLR (< 2.0 vs. ≥ 2.0) was the only independent prognostic factor for poor OS [hazard ratio (HR) = 0.758, 95% confidence intervals (CI) = 0.598-0.960, P = 0.021)] and CSS (HR = 0.738, 95% CI = 0.573-0.950, P = 0.018). Among these inflammatory markers, the c-index and BIC value for NLR were maximum and minimum for OS, respectively. In addition, the c-index was higher and the BIC value was smaller in TNM staging combined with NLR compared with the values obtained in TNM staging alone.Conclusion: NLR is a superior indicator of prognosis compared with LMR, PLR, and PNI in CRC patients, and NLR may serve as an additional indicator based on the current tumor staging system. [ABSTRACT FROM AUTHOR]

Our previous studies showed that the expressions of miR-148a, miR-152 and miR-148b are altered in gastric cancer (GC). The present study aimed to find relationship between individual single nucleotide polymorphisms (SNPs) or haplotypes of these miRNAs and susceptibility, clinicopathological parameters and prognosis of GC in a large sample of the Han population of Northern China. Twelve SNPs were genotyped using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry in a case–control study of 571 Chinese GC patients and 571 cancer-free controls. The rs11170877 G allele (P = 0.027) and the rs12231393 C allele (P = 0.034) were associated with a decreased risk of GC. However, these associations were lost after Bonferroni correction. The rs4719839 G allele was associated with Borrmann type III–IV GC (P = 0.034), increased tumour size (P = 0.020), an increased rate of lymph node metastasis (P = 0.047) and advanced TNM stage (P = 0.009). These associations were also lost after Bonferroni correction. The haplotype of miR-148b was significantly correlated with GC risk. The haplotypes in miRNA-148a were different in Borrmann types. The haplotype of miR-152 distributed various in the positive lymphovascular invasion group compared to negative group. Polymorphisms of miR-148b rs11170877 and 12231393 and their haplotypes were predictive factors of susceptibility to GC. A functional genetic variant of miRNA rs4719839 and the corresponding haplotype were associated with clinicopathological features and prognosis of advanced GCs. [ABSTRACT FROM PUBLISHER]

PROS1 is an encoding gene that can generate protein S. This protein is a glycoprotein found in plasma that conducts physiological functions with vitamin K. However, the impact of its expression remains absent in the progression and prognosis of breast cancer (BC). In this study, we comprehensively explored the expression of PROS1 in BC and its relationship with BC patient survival, prognosis, and other clinicopathological features. We investigated how PROS1 influenced the malignant biological behavior of BC cells. A series of enrichment analyses were conducted, and the immune landscape was explored in BC affected by PROS1. We also determined correlations between PROS1 and common drug sensitivities used for BC treatments. PROS1 had low expression in BC, which tended to result in poor survival of BC patients. Overexpressed PROS1 inhibited the migration and invasion of BC cells as well as the epithelial–mesenchymal transition process by downregulating SNAIL. Functional enrichment analyses revealed that PROS1 was more active in extracellular matrix (ECM) organization and structural constituent, ECM-receptor interaction, and other pathways with its related genes. PROS1 was also found to affect immune activity, including various immune cells infiltrating BC. BC patients with high PROS1 expression tended to have lower IC50 values of three common medications and obtained better efficacy. PROS1 can become a promising prognostic factor and a possible therapeutic target in BC patients and suppress BC cell metastatic potential. In addition, PROS1 is a crucial factor in immune infiltration in BC. • PROS1 is lowly expressed in BC and predicts a poor survival of BC patients. • Overexpressed PROS1 inhibits the migration and invasion of BC cells. • PROS1 is a new hub gene regulating the EMT process and immune infiltration in BC cells. • PROS1 can be a new drug-effect predictor for BC treatment. [ABSTRACT FROM AUTHOR]

• OLR1 was highly upregulated in the breast cancer compared with nontumor tissues. • High expression of OLR1 was significantly correlated with poor prognosis in breast cancer. • OLR1 markedly affected the immune infiltration level of breast cancer. Oxidized low-density lipoprotein receptor 1 (OLR1), a key receptor for oxidized low-density lipoprotein (ox-LDL), plays a crucial role in cancer and inflammatory disease. However, the correlation between OLR1 expression and immune infiltration in breast cancer (BC) remain unclear. In this study, we comprehensively analyzed the expression level of OLR1 in BC tissues and explore the prognostic importance of OLR1 using quantitative real-time PCR, immunohistochemical analysis and different databases. The significantly enriched KEGG and GO pathways were used to identify the potential biological function of OLR1 via LinkedOmics analysis. Furthermore, we detected the correlation between OLR1 expression and a variety of immune infiltrating cells via Tumor Immune Estimation Resource database and GEPIA database. Our study revealed that OLR1 upregulation was observed in BC tissues and correlated with worse clinical outcomes and advanced clinicopathological factors. Meanwhile, OLR1 regulated various immunity-related pathways, especially the polarization of macrophages. Immunohistochemical analysis further confirmed the significant correlation between OLR1 expression and tumor infiltration of M2 macrophages as well as tumor-associated macrophages. OLR1 upregulation indicated poor prognosis in BC, possibly through inducing macrophage polarization and triggering immune evasion. Collectively, OLR1 may represent a potential therapeutic target for BC tailored therapy. [ABSTRACT FROM AUTHOR]