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The relationship between sarcopenia and prognosis in solid organ transplantation recipients (SOTr) remains unverified. We aimed to quantify the prevalence of pretransplant sarcopenia and its effect on patient and graft survival in SOTr. We used PubMed, EMBASE, Cochrane Library and Web of Science to search relevant studies published in English (from inception to December 31, 2021). Prospective and retrospective cohort studies that reported the prevalence of sarcopenia before transplant or the association between sarcopenia and clinical outcomes in SOTr were included. Primary outcomes were the prevalence of sarcopenia and its impact on patient and graft survival. Secondary outcomes included perioperative complications, acute rejection, length of hospital stay, length of intensive care unit stay (ICU LOS) and early readmission. Thirty-nine studies involving 5792 patients were included. Pooled prevalence of sarcopenia amongst SOTr candidates was 40 % (95 % confidence interval [CI]: 34%–47 % and I2 = 97 %). Sarcopenia was associated with increased risk of death (hazard ratio [HR] = 1.87, 95 % CI: 1.46–2.41 and I2 = 60 %), poor graft survival (HR = 1.71, 95 % CI: 1.16–2.54 and I2 = 57 %) and increased liver graft loss (HR = 1.43, 95 % CI: 1.03–1.99 and I2 = 38 %). Patients with sarcopenia demonstrated increased incidence of perioperative complications (risk ratio [RR] = 1.34, 95 % CI: 1.17–1.53 and I2 = 40 %), long ICU LOS (mean difference = 2.31 days, 95 % CI: 0.58–4.04 and I2 = 97 %) and decreased risk of acute rejection (RR = 0.61, 95 % CI: 0.42–0.89 and I2 = 0 %). In Conclusion, sarcopenia is prevalent in SOTr candidates and associated with death and graft loss. Identifying sarcopenia before transplantation and intervening may improve long-term outcomes.

Accumulating evidence suggests that aging and senescence play crucial roles in tumorigenesis, cancer progression, and treatment. However, the influence of aging and senescence-related genes (ASRGs) on clinical outcomes and treatment options in lung adenocarcinoma (LUAD) patients remains unknown. Here, we developed an aging and senescence-related scoring system, ASRS, by integrating bulk transcriptome data from 22 LUAD datasets. In 3,243 LUAD samples, higher ASRS scores were associated with poor tumor stage and pathological grade, as well as shorter overall survival, disease-free survival, and recurrence-free survival. Additionally, ASRS was associated with different immune patterns in the tumor microenvironment (TME). Importantly, ASRS was found to predict therapeutic efficacy, with patients having a low ASRS benefiting from immunotherapy and those with a high ASRS responding better to chemotherapy. Therefore, ASRS represents a previously overlooked characteristic of LUAD that can influence patient outcomes and treatment success.

PurposePediatric testicular yolk sac tumor is a rare malignant germ cell tumor and there is a lack of large clinical studies. The purpose of this study is to summarize the clinical characteristics of pediatric testicular yolk tumor and evaluate the prognostic factors.Materials and methodsThe medical records of children with testicular yolk sac tumor in one pediatric medical centre in China from January 2005 to January 2021 were retrospectively investigated. Data regarding clinical characteristics, treatment and prognosis were collected.ResultsA total of 109 patients with a median diagnosed age of 18 months (range 2–69) were included in this study; of them 100 were diagnosed as stage I, 6 as stage II and 3 as stage IV. All patients underwent radical orchiectomy, and 61 of them underwent postoperative chemotherapy. The mean follow-up time was 61.3 months (range 3–259), during that time, 8 patients experienced relapse. The five-year overall survival was 90.6% (95% CI 84.6%–96.7%). Univariate Cox regression analysis showed that disease stage, relapse, maximum tumor diameter, and alpha-fetoprotein returning to normal within 2 months postoperatively were risk factors for survival (HRs of 25.43, 26.43, 1.48 and 0.08, respectively, p

Wilms tumour (WT) is the most common kidney malignancy in children. Chemoresistance is the leading cause of tumour recurrence and poses a substantial therapeutic challenge. Increasing evidence has underscored the role of the tumour immune microenvironment (TIM) in cancers and the potential for immunotherapy to improve prognosis. There remain no reliable molecular markers for reflecting the immune landscape and predicting patient survival in WT. Here, we examine differences in gene expression by high-throughput RNA sequencing, focused on differentially expressed immune-related genes (IRGs) based on the ImmPort database. Via univariate Cox regression analysis and Lasso-penalized Cox regression analysis, IRGs were screened out to establish an immune signature. Kaplan-Meier curves, time-related ROC analysis, univariate and multivariate Cox regression studies, and nomograms were used to evaluate the accuracy and prognostic significance of this signature. Furthermore, we found that the immune signature could reflect the immune status and the immune cell infiltration character played in the tumour microenvironment (TME) and showed significant association with immune checkpoint molecules, suggesting that the poor outcome may be partially explained by its immunosuppressive TME. Remarkably, TIDE, a computational method to model tumour immune evasion mechanisms, showed that this signature holds great potential for predicting immunotherapy responses in the TARGET-wt cohort. To decipher the underlying mechanism, GSEA was applied to explore enriched pathways and biological processes associated with immunophenotyping and Connectivity map (CMap) along with DeSigN analysis for drug exploration. Finally, four candidate immune genes were selected, and their expression levels in WT cell lines were monitored via qRT-PCR. Meanwhile, we validated the function of a critical gene, NRP2. Taken together, we established a novel immune signature that may serve as an effective prognostic signature and predictive biomarker for immunotherapy response in WT patients. This study may give light on therapeutic strategies for WT patients from an immunological viewpoint.

Circular RNA (circRNA), which is a newly discovered non-coding RNA, has been documented to play important roles in miRNA sponges, and the dysregulation of which is involved in cancer development. However, circRNA expression profiles and their role in initiation and progression of Wilms tumor (WT) remain largely unclear at present. Here, we used paired WT samples and high-throughput RNA sequencing to identify differentially expressed circRNAs (DE-circRs) and mRNAs (DE-mRs). A total of 314 DE-circRs and 1612 DE-mRs were identified. The expression of a subset of differentially expressed genes was validated by qRT–PCR. A complete circRNA-miRNA-mRNA network was then constructed based on the common miRNA targets of DE-circRs and DE-mRs identified by miRanda prediction tool. The Gene set enrichment analysis (GSEA) indicated that several signaling pathways involving targeted DE-mRs within the ceRNA network were associated with cell cycle and immune response, which implies their participation in WT development to some extent. Subsequently, these targeted DE-mRs were subjected to implement PPI analysis and to identify 10 hub genes. Four hub genes were closely related to the survival of WT patients. We then filtered prognosis-related hub genes by Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a prognosis-related risk score system based on a three-gene signature, which showed good discrimination and predictive ability for WT patient survival. Additionally, we analyzed the mutational landscape of these genes and the associations between their expression levels and those of immune checkpoint molecules and further demonstrated their potential impact on the efficacy of immunotherapy. qRT–PCR and western blotting (WB) analysis were used to validate key differentially expressed molecules at the RNA and protein levels, respectively. Besides these, we selected a key circRNA, circEYA1, for function validation. Overall, the current study presents the full-scale expression profiles of circRNAs and the circRNA-related ceRNA network in WT for the first time, deepening our understanding of the roles and downstream regulatory mechanisms of circRNAs in WT development and progression. We further constructed a useful immune-related prognostic signature, which could improve clinical outcome prediction and guide individualized treatment.

Background: Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME). However, the relationships between acetylation-related genes, patient prognosis, and the tumour immune microenvironment (TIME) are not yet understood. Our research aims to investigate the link between acetylation and the tumour microenvironment, with the goal of identifying new biomarkers for estimating survival of patients with EOC. Methods: Using data downloaded from the tumour genome atlas (TCGA), genotypic tissue expression (GTEx), and gene expression master table (GEO), we comprehensively evaluated acetylation-related genes in 375 ovarian cancer specimens and identified molecular subtypes using unsupervised clustering. The prognosis, TIME, stem cell index and functional concentration analysis were compared among the three groups. A risk model based on differential expression of acetylation-related genes was established through minimum absolute contraction and selection operator (LASSO) regression analysis, and the predictive validity of this feature was validated using GEO data sets. A nomogram is used to predict a patient's likelihood of survival. In addition, different EOC risk groups were evaluated for timing, tumour immune dysfunction and exclusion (TIDE) score, stemness index, somatic mutation, and drug sensitivity. Results: We used the mRNA levels of the differentially expressed genes related to acetylation to classify them into three distinct clusters. Patients with increased immune cell infiltration and lower stemness scores in cluster 2 (C2) exhibited poorer prognosis. Immunity and tumourigenesis-related pathways were highly abundant in cluster 3 (C3). We developed a prognostic model for ten differentially expressed acetylation-related genes. Kaplan–Meier analysis demonstrated significantly worse overall survival (OS) in high-risk patients. Furthermore, the TIME, tumour immune dysfunction and exclusion (TIDE) score, stemness index, tumour mutation burden (TMB), immunotherapy response, and drug sensitivity all showed significant correlations with the risk scores. Conclusions: Our study demonstrated a complex regulatory mechanism of acetylation in EOC. The assessment of acetylation patterns could provide new therapeutic strategies for EOC immunotherapy to improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

Recently, studies on competing endogenous RNA (ceRNA) networks have become prevalent, and circular RNAs (circRNAs) have crucial implications for the development and progression of carcinoma. However, studies relevant to metastatic prostate cancer (mPCa) are scant. This study aims to discover potential ceRNAs that may be related to the prognosis of mPCa. RNA-Seq data were obtained from the MiOncoCirc database and Gene Expression Omnibus (GEO). Differential expression patterns of RNAs were examined using R packages. Circular RNA Interactome, miRTarBase, miRDB and TargetScan were applied to predict the corresponding relation between circRNAs, miRNAs and mRNAs. The Gene Ontology (GO) annotations were performed to present related GO terms, and Gene Set Enrichment Analysis (GSEA) tools were applied for pathway annotations. Moreover, survival analysis was conducted for the hub genes. We found 820 circRNAs, 81 miRNAs and 179 mRNAs that were distinguishingly expressed between primary prostate cancer (PCa) and mPCa samples. A ceRNA network including 45 circRNAs, 24 miRNAs and 56 mRNAs was constructed. In addition, the protein–protein interaction (PPI) network was built, and 10 hub genes were selected by using the CytoHubba application. Among the 10 hub genes, survival analysis showed that ITGA1, LMOD1, MYH11, MYLK, SORBS1 and TGFBR3 were significantly connected with disease-free survival (DFS). The circRNA-mediated ceRNA network provides potential prognostic biomarkers for metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlations between the habit of betel quid and areca nut (BQ‐AN) chewing and the prognosis of oral cancer (OC). Methods: We performed a systematic review and meta‐analysis to clarify this issue. Data searches were performed using PubMed, Web of Science, Epistemonikos, and Embase databases through November 2019. The primary outcome was the difference in the prognosis of OC between BQ‐AN chewers and non‐chewers, measured in terms of 5‐year overall survival (OS) and 5‐year disease‐specific survival (DSS) log (HR) reported in articles. The pooled HR with 95% CI of 5‐year OS and 5‐year DSS was calculated using a fixed‐effects model. Results: Ten articles with eleven OS or DSS survival studies (one of the articles contained two studies), which were published between 2003 and 2017, were eligible for inclusion in the present study. All the 11 studies were observational studies, among which 10 were retrospective and 1 was prospective. One study measured both OS and DSS. Eight studies, with a total of 2,761 patients, used 5‐year OS as the primary endpoint and four studies, with a total of 2,551 patients, used 5‐year DSS. Overall, the pooled HR evaluating BQ‐AN chewers was 1.26 (95% CI: 1.09–1.46) for 5‐year OS and 1.40 (95% CI: 1.15–1.70) for 5‐year DSS, compared with non‐chewers. There was a significant association between BQ‐AN chewing and OC survival. Conclusions: Betel quid and areca nut chewing is significantly associated with poor prognosis in patients with OC. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared the etiology and clinical features between pure lateral medullary infarction (LMI) and pure medial medullary infarction (MMI). Methods: All patients included were hospitalized at The First Affiliated Hospital and The Second Affiliated Hospital of Wenzhou Medical University from January 2015 to July 2020. Their risk factors, clinical manifestation, stroke mechanisms and short‐term prognosis were analyzed retrospectively. Results: Among the 387 patients enrolled, 266 (68.7%) had LMI, 109 (28.2%) had MMI, and 12 (3.1%) (nine men and three women) had LMI plus MMI. We analyzed the 375 patients of LMI and MMI. The average ages of LMI and MMI were 59.4 years and 62.69 years, respectively. Univariate analysis and multivariable logistic regression was used to investigate the existing risk factors of MMI relative to LMI. Prior infarction, poor glycemic control, and atherosclerosis were more frequently associated with MMI than with LMI. The clinical manifestation was significantly different between LMI and MMI. We used modified Rankin Scale (mRS) score as the short‐term prognostic evaluation criteria, and MMI appeared worse than LMI. Conclusions: This study reveals that: (1) patients with MMI are older than those with LMI; (2) prior infarction, poor glycemic control, and atherosclerosis are independent risk factors of MMI than that of LMI; (3) the clinical manifestations of LMI and MMI are heterogeneous; (4) short‐term prognosis of MMI is worse than LMI. [ABSTRACT FROM AUTHOR]

PurposeThis study aimed to investigate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting early immunotherapy response of immune checkpoint inhibitors (ICIs) in patients with advanced or metastatic non-small-cell lung cancer (NSCLC).MethodsA comprehensive search of PubMed, Web of science, Embase and the Cochrane library was performed to examine the prognostic value of 18F-FDG PET/CT in predicting early immunotherapy response of ICIs in patients with NSCLC. The main outcomes for evaluation were overall survival (OS) and progression-free survival (PFS). Detailed data from each study were extracted and analyzed using STATA 14.0 software.Results13 eligible articles were included in this systematic review. Compared to baseline 18F-FDG PET/CT imaging, the pooled hazard ratios (HR) of maximum and mean standardized uptake values SUVmax, SUVmean, MTV and TLG for OS were 0.88 (95% CI: 0.69-1.12), 0.79 (95% CI: 0.50-1.27), 2.10 (95% CI: 1.57-2.82) and 1.58 (95% CI: 1.03-2.44), respectively. The pooled HR of SUVmax, SUVmean, MTV and TLG for PFS were 1.06 (95% CI: 0.68–1.65), 0.66 (95% CI: 0.48-0.90), 1.50 (95% CI: 1.26-1.79), 1.27 (95% CI: 0.92-1.77), respectively. Subgroup analysis showed that high MTV group had shorter OS than low MTV group in both first line group (HR: 1.97, 95% CI: 1.39-2.79) and undefined line group (HR: 2.11, 95% CI: 1.61-2.77). High MTV group also showed a shorter PFS in first line group (HR: 1.85, 95% CI: 1.28-2.68), and low TLG group had a longer OS in undefined group (HR: 1.37, 95% CI: 1.00-1.86). No significant differences were in other subgroup analysis.ConclusionBaseline MTV and TLG may have predictive value and should be prospectively studied in clinical trials. Baseline SUVmax and SUVmean may not be appropriate prognostic markers in advanced or metastatic NSCLC patients treated with ICIs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323906, identifier CRD42022323906.