Deng-Xiong Li

To identify chromatin regulators (CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence (BCR) after radical prostatectomy (RAP) in prostate cancer (PCa) patients. Differentially expressed genes (DEGs) between tumor and normal samples from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) databases were intersected with CR-related and prognostic genes. Consensus clustering, risk score analysis, functional analysis, immune microenvironment, m6A, and heterogeneity assessments were performed using R software. In vitro validation used DU145 and C42B PCa cell lines. Topoisomerase II alpha (TOP2A) was knocked down via siRNA. Assays included CCK-8 proliferation, colony formation, transwell migration/invasion, wound healing, and western blotting (WB) for pathway validation. TOP2A and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) defined molecular subtypes and a risk score in TCGA, validated in a GEO dataset. Cluster 2 exhibited significantly shorter BCR-free survival vs. cluster 1 in TCGA [hazard ratio (HR): 2.21; 95% confidence interval (95% CI): 1.32−3.73; P=0.003)], GEO (HR: 2.05; 95% CI: 1.05−4.02; P=0.010), and MSKCC2010 (HR: 5.93; 95% CI: 1.96−17.87; P<0.001). Similar survival differences were observed between high- and low-risk groups (defined by the median risk score). Cluster 2 showed greater tumor heterogeneity and higher m6A gene expression. Gene set variation analysis (GSVA) revealed downregulated cell-cycle pathways in cluster 2, alongside suppressed tumor-infiltrating immune cells. TOP2A knockdown significantly impaired PCa cell proliferation, colony formation, migration, and invasion. Mechanistically, it suppressed phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) pathway activation, reducing phosphorylated PI3K and AKT levels without altering total protein. TOP2A and PPARGC1A effectively stratify PCa subtypes for RAP patients. TOP2A drives malignant progression via the PI3K/AKT pathway.

Background Recent studies have established a correlation between ADAMTSL2 (ADAMTS-like 2) and the development of various cancers. This study aims to conduct a comprehensive pan-cancer analysis in 37 cancer types and investigate its potential role in colon and rectal adenocarcinoma (COADREAD). Method Pan-cancer and mutation data were sourced from The Cancer Genome Atlas (TCGA) database and analyzed using Sangerbox analysis platform. We explored the expression patterns and prognostic implications of ADAMTSL2, and investigated its relationships with tumor heterogeneity, stemness, immune checkpoint genes, immune cell infiltration, RNA modifications, and mutational profiles across different cancers. Additionally, with Ethics Committee approval, we conducted immunohistochemical (IHC) analysis on 120 COADEAD samples to evaluate ADAMTSL2 expression and its association with clinicopathological parameters. Results ADAMTSL2 expression was positively correlated with the hazard ratio of OS, DSS, DFI and PFI for ESCA and COADREAD. A negative correlation was observed between ADAMTSL2 expression and NEO levels in COAD. Gene alterations in ADAMTSL2 were observed, with a mutation frequency of 5.0% in COAD. There is a significant correlation between ADAMTSL2 expression and immune cell infiltration in a variety of cancers. The expression level of ADAMTSL2 protein was associated with T stage, N stage, M stage (p < 0.05). Kaplan‒Meier survival curves demonstrated that the high ADAMTSL2 group had a shorter OS time (p = 0.047) and progression free survival time (p = 0.026) than the low ADAMTSL2 group. Conclusion In summary, we conducted a comprehensive pan-cancer analysis of ADAMTSL2 and we demonstrated that ADAMTSL2 may serve as a novel prognostic biomarker and immunotherapy target in COADREAD.

Background: Repeat transurethral resection of bladder tumour (reTURB) is a conventional treatment for non-muscle-invasive bladder cancer (NMIBC) to enhance prognosis. However, the necessity of reTURB in NMIBC remains controversial owing to upstaging of treatments and new evidence. Objectives: We performed an umbrella review to determine the need for reTURB in patients with NMIBC. Design: We extracted data from meta-analyses that were screened out after a systematic search of PubMed, Embase, the Web of Science and the Cochrane Database of Systematic Reviews. Methods: Risk of Bias in Systematic Reviews and the Grading of Recommendations, Assessment, Development and Evaluation tools were used to assess the quality of each included meta-analysis and outcomes. Results: Our study included seven meta-analyses. Two studies assessed the efficiency of reTURB in patients who underwent en bloc resection of bladder tumours (ERBT). Patients who underwent ERBT reported low residual tumour and upstaging rates of 5.9% and 0.3%, respectively. Conversely, patients who underwent conventional transurethral resection for bladder cancer (cTURB) had high residual tumour rates. Patients who underwent cTURB and reTURB had significantly improved 1-year recurrence-free survival (RFS) compared to those who underwent initial cTURB alone. In terms of progression-free survival (PFS), a meta-analysis reported that patients who underwent cTURB and reTURB had significantly improved PFS compared with those who underwent initial cTURB alone. In the subgroup analyses of ERBT, reTURB did not affect the RFS and PFS of patients who received ERBT. Currently, only a limited number of randomised clinical trials have evaluated reTURB, and various factors have influenced its efficacy. Conclusion: There was significant variation in survival outcomes among patients undergoing reTURB. The necessity and efficacy of reTURB depend on numerous factors, such as surgical approach, equipment and medication usage. Patients eligible for ERBT may constitute a group that does not require reTURB. Further clinical trials are required to validate these findings. Registration: This umbrella review was registered with the International Prospective Register of Systematic Reviews (CRD42023439078).

Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71–2.02; I² = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41–3.07; I² = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.