Vasculogenic mimicry-related gene prognostic index for predicting prognosis, immune microenvironment in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a highly aggressive cancer associated with higher death rates. However, traditional anti-angiogenic therapies have limited effectiveness due to drug resistance. Vascular mimicry (VM) provides a different way for tumors to develop blood vessels without relying on endothelial cells or angiogenesis. However, the intricate mechanisms and interplay between it and the immune microenvironment in ccRCC remain unclear. Methods: A PubMed and GeneCards literature review was conducted to identify VM-related genes (VMRGs). VMRGs expression profiles were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), developing a novel VM risk score model and nomogram for ccRCC. The EBI ArrayExpress database (the validation set) was obtained to validate the prognostic model. The relationship between VMRGs risk score clinical characteristics and immune infiltration was investigated. Finally, the expression of six model VMRGs was validated using single-cell analysis, GEPIA, Human Protein Atlas (HPA), and quantitative Real-time PCR (qRT-PCR). Results: Cox regression analysis and nomogram identified L1CAM, TEK, CLDN4, EFNA1, SERPINF1, and MALAT1 as independent prognostic risk factors, which could be used to stratify the ccRCC population into two risk groups with distinct immune profiles and responsiveness to immunotherapy. The results of single-cell analysis, GEPIA, HPA, and qRT-PCR validated the model genes' expression. Conclusions: Our novel findings constructed a convenient and reliable 6 gene signatures as potential immunologic and prognostic biomarkers of VM in ccRCC.

[Prognostic factors of patients with muscle invasive bladder cancer with intermediate-to-high risk prostate cancer].

OBJECTIVE: To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer (MIBC) with intermediate-to-high-risk primary prostate cancer. METHODS: From January 2012 to October 2023, the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed. All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study. Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients. For significant influencing factors (pathological T stage, M stage and perineural invasion of bladder cancer), survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors. RESULTS: A total of 32 patients were included in this study. The mean age was (72.5±6.6) years; the median preoperative total prostate specific antigen (tPSA) was 6.68 (2.47, 6.84) µg/L; the mean preoperative creatinine was (95±36) µmol/L, and the median survival time was 65 months. The majority of the patients (87.5%) had high-grade bladder cancer, 53.1% had lymphatic invasion, and 31.3% had perineural invasion. Prostate involvement was observed in 25.0% of the cases, and the positive rate of soft-tissue surgical margin was 37.5%. Multivariate Cox analysis revealed that preoperative creatinine level (HR=1.02, 95%CI: 1.01-1.04), pathological stage of bladder cancer T3 (HR=11.58, 95%CI: 1.38-97.36) and T4 (HR=19.53, 95%CI: 4.26-89.52) metastasis of bladder cancer (HR=9.44, 95%CI: 1.26-70.49) and perineural invasion of bladder cancer (HR=6.26, 95%CI: 1.39-28.27) were independent prognostic factors (P < 0.05). Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3, T4, M1, and perineural invasion were unfavorable factors affecting the patients' survival prognosis (P < 0.05). CONCLUSION: Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis. High preoperative serum creatinine, T3 or T4 pathological stage of bladder cancer, metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.

Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

OBJECTIVES: Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). METHODS: This study included young adult patients aged 18-40 years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. RESULTS: A total of 300 RCC patients aged 18-40 years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4 ± 6.1 years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p < 0.001). There was no statistically significant difference observed in overall survival (OS) (p = 0.069). Pathological stage was a significant independent predictor for OS (p = 0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p = 0.020; p = 0.005). CONCLUSIONS: The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Causal inference between rheumatoid arthritis and prostate cancer.

It is unclear if the association between rheumatoid arthritis (RA) and a higher risk of prostate cancer (Pca) reflects a causal relationship. We conducted a meta-analysis and used the Mendelian randomization method (MR) to evaluate the association between RA and Pca risk. A meta-analysis and subgroup analysis of the incidence of Pca in patients with RA was conducted. To determine whether genetically elevated RA levels were causally linked to Pca, two MR samples were employed. To eliminate gender-related bias, we conducted a stratified analysis of the GWAS data for RA by gender, specifically including 140,254 males. Additional MR analysis was also performed to determine potential confounding factors influencing the association between genetically susceptible RA and Pca. In total, 409,950 participants were enrolled in 20 trials to investigate the Pca risk in patients with RA. The meta-analysis suggested that RA was unrelated to the Pca risk (SIR = 1.072, 95% CI, 0.883-1.261). However, a subgroup analysis showed that low smoking rates might increase the Pca risk in patients with RA by 24%. The MR analysis showed that increased genetic susceptibility to RA was related to a high Pca risk (OR = 36.20, 95%CI = 1.24-1053.12, P = 0.037). The causality estimation of MR-Egger, Weighted mode, Simple mode, and Weighted median method were similar in direction and magnitude. Although our meta-analysis found no correlation between RA and Pca risk, MR analyses supported a causal relationship between genetic susceptibility to RA and increased prostate risk. Early attention to Pca risk in patients with RA may be important for improving prognosis and mortality in such patients. Further research is needed to determine the etiology of RA attributed to Pca and its underlying mechanisms.

Systemic lupus erythematosus and prostate cancer risk: a pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Current observational studies suggest that there may be a causal relationship between systemic lupus erythematosus (SLE) and prostate cancer (PC). However, there is contradictory evidence. This study aimed to investigate and clarify the association between SLE and PC. METHODS: We searched PubMed, Embase, Web of Science, and Scopus until May 2022. A meta-analysis was conducted on the standard incidence rate (SIR) and 95% CI. Subgroup analysis was performed based on the follow-up duration, study quality, and appropriate SLE diagnosis. Mendelian randomization (MR) of the two samples was used to determine whether genetically elevated SLE was causal for PC. Summary MR data were obtained from published GWASs, which included 1,959,032 individuals. The results were subjected to sensitivity analysis to verify their reliability. RESULTS: In a meta-analysis of 79,316 participants from 14 trials, we discovered that patients with SLE had decreased PC risk (SIR, 0.78; 95% CI, 0.70-0.87) significantly. The MR results showed that a one-SD increase in genetic susceptibility to SLE significantly reduced PC risk (OR, 0.9829; 95% CI, 0.9715-0.9943; P = 0.003). Additional MR analyses suggested that the use of immunosuppressants (ISs) (OR, 1.1073; 95% CI, 1.0538-1.1634; P < 0.001), but not glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs), which were associated with increased PC risk. The results of the sensitivity analyses were stable, and there was no evidence of directional pleiotropy. CONCLUSIONS: Our results suggest that patients with SLE have a lower risk of developing PC. Additional MR analyses indicated that genetic susceptibility to the use of ISs, but not GCs or NSAIDs, was associated with increased PC risk. This finding enriches our understanding of the potential risk factors for PC in patients with SLE. Further study is required to reach more definitive conclusions regarding these mechanisms.

Evaluation of efficacy of rituximab for membranous nephropathy: A systematic review and meta-analysis of 11 studies.

INTRODUCTION: The use of traditional immunosuppressive medicines for the treatment of membranous nephropathy is being challenged, owing to its limited efficacy and tolerability. Research on M-type phospholipase A2 receptor antibodies has provided a new way for evaluating the efficiency and prognosis of treatment of membranous nephropathy. However, the relationship between rituximab, a monoclonal antibody against CD20, and antiphospholipase A2 receptor antibodies and the drug regimen of rituximab for membranous nephropathy is uncertain. We conducted a meta-analysis to evaluate the efficacy of rituximab treatments in membranous nephropathy and compared the clinical effects of first-line and second-line rituximab therapies. METHODS: PubMed, Embase, Web of Science, Scopus, the Cochrane Central Register ofControlled Trials, and ClinicalTrials.gov were searched to find articles about rituximab treatment of patients with membranous nephropathy between January 2000 and August 2020. The outcomes included remission, antiphospholipase A2 receptor antibodies, relapse, and adverse events. The Grading of Recommendations Assessment Development and Evaluation criteria were used to evaluate the strength of evidence. RESULTS: A total of 723 participants from 11 trials were included in this meta-analysis. The other treatments included cyclosporine, cyclophosphamide, steroids, and non-immunosuppressive antiproteinuric treatment. Rituximab significantly improved cumulative remission (P=0.007; Odds Ratio [OR]=3.06; 95% confidence interval [CI]=1.35-6.94) compared with other treatments. It significantly reduced relapse (P<0.00001; OR=0.06; 95% CI=0.02-0.19), antiphospholipase A2 receptor antibody levels (P=0.0009; SMD=-0.52; 95% CI=-0.83 to -0.21), and the proportion of patients positive for anti-PLA2R antibodies (P=0.003; OR=6.11; 95% CI=1.85-20.24) compared with other treatments. Compared with the second-line, first-line rituximab therapy achieved a higher rate of cumulative remission (P=0.03; OR=0.32, 95% CI=0.11-0.91). CONCLUSIONS: Rituximab can improve the rate of clinical remission in patients with membranous nephropathy. Rituximab was more effective than other treatments in reducing relapse, antiphospholipase A2 receptor antibody levels, and the proportion of patients positive for antiphospholipase A2 receptor antibodies. The clinical remission rate following first-line rituximab therapy was better than that of second-line rituximab therapy for membranous nephropathy.