Comprehensive analysis of macrophage-related genes in prostate cancer by integrated analysis of single-cell and bulk RNA sequencing.

Macrophages, as essential components of the tumor immune microenvironment (TIME), could promote growth and invasion in many cancers. However, the role of macrophages in tumor microenvironment (TME) and immunotherapy in PCa is largely unexplored at present. Here, we investigated the roles of macrophage-related genes in molecular stratification, prognosis, TME, and immunotherapeutic response in PCa. Public databases provided single-cell RNA sequencing (scRNA-seq) and bulk RNAseq data. Using the Seurat R package, scRNA-seq data was processed and macrophage clusters were identified automatically and manually. Using the CellChat R package, intercellular communication analysis revealed that tumor-associated macrophages (TAMs) interact with other cells in the PCa TME primarily through MIF - (CD74+CXCR4) and MIF - (CD74+CD44) ligand-receptor pairs. We constructed coexpression networks of macrophages using the WGCNA to identify macrophage-related genes. Using the R package ConsensusClusterPlus, unsupervised hierarchical clustering analysis identified two distinct macrophage-associated subtypes, which have significantly different pathway activation status, TIME, and immunotherapeutic efficacy. Next, an 8-gene macrophage-related risk signature (MRS) was established through the LASSO Cox regression analysis with 10-fold cross-validation, and the performance of the MRS was validated in eight external PCa cohorts. The high-risk group had more active immune-related functions, more infiltrating immune cells, higher HLA and immune checkpoint gene expression, higher immune scores, and lower TIDE scores. Finally, the NCF4 gene has been identified as the hub gene in MRS using the "mgeneSim" function.

A prognostic cuproptosis-related lncRNA predictive signature for bladder cancer patients.

Cuproptosis is a novel form of cell death in tumours. However, the clinical impact and mechanism of cuproptosis in bladder cancer (BC) remain unclear. This study aimed to explore the functions of long noncoding RNAs (lncRNAs) related to cuproptosis in BC and develop a prognostic predictive model. RNA sequencing and clinicopathological data were derived from The Cancer Genome Atlas and randomly divided into training and validation groups. Cuproptosis-related lncRNAs were identified by Cox regression analysis and least absolute shrinkage and selection operator, and the patients were divided into high- and low-risk groups according to the median value of the signature-based risk score. We established a signature of 17 cuproptosis-associated lncRNAs in the training set. In both sets, patients with higher signature-based risk scores had a notably higher probability of death (P ≤ 0.001) and a shorter survival duration. Cox regression analyses confirmed the risk score as an independent predictor of BC prognosis in the entire set. The area under the curve (AUC) values for 1-, 3-, and 5-year survival were 0.767, 0.734, and 0.764, respectively, confirming that the signature could determine the prognosis of BC. A signature-based nomogram was developed, and its prediction accuracy was validated using calibration curves. Several drugs, including Gemcitabine, Oxaliplatin, Mitoxantrone, Camptothecin, Cytarabine and Irinotecan may benefit low-risk BC patients more. Finally, in vitro experiments confirmed that the cuproptosis-related lncRNAs are highly expressed in bladder cancer cells after cuproptosis induced by exogenous copper ions. In conclusion, a cuproptosis-related lncRNA signature independently predicted prognosis in BC, indicating a possible mechanism and clinical treatment approach.

Construction and validation of a novel cuproptosis-related long noncoding RNA signature for predicting the outcome of prostate cancer.

Background: Prostate cancer (PCa) is one of the most common tumors of the urinary system. Cuproptosis is a novel mode of controlled cell death that is related to the development of various tumor types. However, the functions of cuproptosis-related long noncoding RNAs (CRLs) in PCa have not yet been well studied. Methods: In this study, data of PCa patients were obtained from The Cancer Genome Atlas (TCGA) and from the Changhai Hospital. Univariate and multivariate Cox regression analyses and LASSO regression analysis were conducted to screen CRLs linked to the prognosis of PCa patients. A risk score model was constructed on the basis of CRLs to predict prognosis. PCa patients were categorized into high- and low-risk cohorts. The predictive value of the risk score was evaluated by Kaplan-Meier survival analysis, receiver operating characteristic curves, and nomograms. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore possible pathways involving CRLs in PCa. Immune function analysis confirmed the correlation between CRLs and immunity in PCa. Finally, we explored the tumor mutational burden and drug response in the high- and low-risk cohorts. Results: First, we identified seven CRLs (C1orf229, C9orf139, LIPE-AS1, MCPH1-AS1, PRR26, SGMS1-AS1, and SNHG1) that were closely related to prognosis in PCa. The risk score model based on the selected CRLs could accurately predict the prognosis of PCa patients. The high-risk cohort was associated with worse disease-free survival (DFS) time in PCa patients (p < 0.001). ROC curve analysis was performed to confirm the validity of the signature (area under the curve (AUC) at 1 year: 0.703). Nomograms were constructed based on the risk score and clinicopathological features and also exhibited great predictive efficiency for PCa. GO and KEGG analyses showed that the CRLs were mainly enriched in metabolism-related biological pathways in PCa. In addition, immune function analysis showed that patients in the high-risk cohort had higher TMB and were more sensitive to conventional chemotherapy and targeted drugs including doxorubicin, epothilone B, etoposide, and mitomycin C. Conclusion: We constructed a novel CRL-related risk score model to accurately predict the prognosis of PCa patients. Our results indicate that CRLs are potential targets for drug therapy in PCa and provide a possible new direction for personalized treatment of PCa patients.

Is There an Association Between Hypothyroidism and Sexual Dysfunction: A Systematic Review and Cumulative Analysis.

INTRODUCTION: Many investigators have found a detrimental effect on sexual functioning developed by hypothyroidism in both sexes, but a cumulative analysis has not been conducted. AIM: This study aims to summarize and quantify the association between overt or subclinical hypothyroidism and the risk of sexual dysfunction (SD) through a meta-analysis. METHODS: 4 electronic databases were systematically searched. The quality of evidence was rated by the GRADE approach. This meta-analysis was registered on the PROSPERO (ID: CRD42020186967). MAIN OUTCOME MEASURE: The strength of the relationship between overt/subclinical hypothyroidism and SD was quantified by presenting the relative risk (RR) with its 95% confidence interval (CI). RESULTS: 7 studies involving 460 patients with hypothyroidism and 2,143 healthy controls were included in this meta-analysis. Among the 7 included studies, 2 studies were provided the data of both overt and subclinical hypothyroidism. Pooled results from 4 included studies investigating overt hypothyroidism indicated that overt hypothyroidism led to significant SD in both sexes (RR = 2.26, 95% CI: 1.42 to 3.62, P = 0.001), while synthetic RR of 5 eligible studies reporting subclinical hypothyroidism failed to find a positive association between subclinical hypothyroidism and SD (RR = 1.3, 95% CI: 0.85 to 1.99, P = 0.229), irrespective of gender (all P > 0.05). Subgroup analyses revealed that women with overt hypothyroidism rather than men with overt hypothyroidism were correlated with a significant higher risk of SD. The quality of evidence in the study of overt hypothyroidism and subclinical hypothyroidism was considered low and moderate, respectively. CONCLUSION: SD is a devastating problem in female patients with clinical hypothyroidism but insusceptible in either women or men with subclinical hypothyroidism. Clinicians should be aware of these phenomena and manage the sufferers accordingly in clinical practice. More rigorous studies are still needed to validate this evidence. Shen M, Li X, Wu W, et al. Is There an Association Between Hypothyroidism and Sexual Dysfunction: A Systematic Review and Cumulative Analysis. Sex Med 2021;9:100345.