PurposeThis study aimed to construct an m6A-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using data obtained from The Cancer Genome Atlas (TCGA) database.MethodsThe KIRC patient data were downloaded from TCGA database and m6A-related genes were obtained from published articles. Pearson correlation analysis was implemented to identify m6A-related lncRNAs. Univariate, Lasso, and multivariate Cox regression analyses were used to identifying prognostic risk-associated lncRNAs. Five lncRNAs were identified and used to construct a prognostic signature in training set. Kaplan–Meier curves and receiver operating characteristic (ROC) curves were applied to evaluate reliability and sensitivity of the signature in testing set and overall set, respectively. A prognostic nomogram was established to predict the probable 1-, 3-, and 5-year overall survival of KIRC patients quantitatively. GSEA was performed to explore the potential biological processes and cellular pathways. Besides, the lncRNA/miRNA/mRNA ceRNA network and PPI network were constructed based on weighted gene co-expression network analysis (WGCNA). Functional Enrichment Analysis was used to identify the biological functions of m6A-related lncRNAs.ResultsWe constructed and verified an m6A-related lncRNAs prognostic signature of KIRC patients in TCGA database. We confirmed that the survival rates of KIRC patients with high-risk subgroup were significantly poorer than those with low-risk subgroup in the training set and testing set. ROC curves indicated that the prognostic signature had a reliable predictive capability in the training set (AUC = 0.802) and testing set (AUC = 0.725), respectively. Also, we established a prognostic nomogram with a high C-index and accomplished good prediction accuracy. The lncRNA/miRNA/mRNA ceRNA network and PPI network, as well as functional enrichment analysis provided us with new ways to search for potential biological functions.ConclusionsWe constructed an m6A-related lncRNAs prognostic signature which could accurately predict the prognosis of KIRC patients.
Objective: To evaluate the safety and oncological outcomes of laparoscopic colorectal surgery using natural orifice specimen extraction (NOSE) compared with conventional laparoscopic (CL) colorectal surgery in patients with colorectal diseases. Methods: We conducted a systematic search of PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), prospective non-randomized trials and retrospective trials up to September 1, 2018, and used 5-year disease-free survival (DFS), lymph node harvest, surgical site infection (SSI), anastomotic leakage, and intra-abdominal abscess as the main endpoints. Subgroup analyses were conducted according to the different study types [RCT and NRCT (non-randomized controlled trial)]. A sensitivity analysis was carried out to evaluate the reliability of the outcomes. RevMan5.3 software was used for statistical analysis. Results: Fourteen studies were included (two RCTs, seven retrospective trials and five prospective non-randomized trials) involving a total of 1,435 patients. Compared with CL surgery, the NOSE technique resulted in a shorter hospital stay, shorter time to first flatus, less post-operative pain, and fewer SSIs and total perioperative complications. Anastomotic leakage, blood loss, and intra-abdominal abscess did not differ between the two groups, while operation time was longer in the NOSE group. Oncological outcomes such as proximal margin [weighted mean difference [WMD] = 0.47; 95% confidence interval [CI] −0.49 to 1.42; P = 0.34], distal margin (WMD= −0.11; 95% CI −0.66 to 0.45; P = 0.70), lymph node harvest (WMD = −0.97; 95% CI −1.97 to 0.03; P = 0.06) and 5-year DFS (hazard ratio = 0.84; 95% CI 0.54–1.31; P = 0.45) were not different between the NOSE and CL surgery groups. Conclusions: Compared with CL surgery, NOSE may be a safe procedure, and can achieve similar oncological outcomes. Large multicenter RCTs are needed to provide high-level, evidence-based results in NOSE-treated patients and to determine the risk of local recurrence.
Objective: The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer (mCRPC) under different treatment options (chemotherapy, hormone therapy). Methods: We conducted a systematic search of PubMed, EMBASE and Cochrane databases for clinical studies up to June 4, 2021, and used prostate-specific antigen (PSA) progression free-survival (PSA-PFS), radiologic PFS (r-PFS), overall survival (OS) and PSA response rate (PSA RR) as the main endpoints. Subgroup analyses were conducted based on the source of the specimens. STATA v.15 software was used for data analysis. Results: Twenty-one studies were included in this meta-analysis, with a total of 1578 samples. In the abiraterone (AA)/enzalutamide (E) treatment group, AR-V7 positive patients had worse PSA-PFS (hazard ratio [HR] = 3.40; 95% confidence interval [95%CI] 2.56-4.51; P < 0.05) and worse r-PFS (HR = 2.69; 95%CI 1.70-4.24; P < 0.05) and OS (HR = 3.02; 95%CI 1.73-5.30; P < 0.05). Multivariate Cox regression results showed that AR-V7 positive status was an independent risk factor for OS in the AA/E treatment group. In the taxane treatment group, AR-V7-positive and negative patients had similar PSA-PFS (HR = 0.87; 95%CI 0.46-1.63; P = 0.657), r-PFS (HR = 1.01; 95%CI 0.53-1.96; P = 0.965) and OS (HR = 1.50; 95%CI 0.89-2.52; P = 0.127). For AR-V7-positive patients, the difference in OS between taxane and AA/E treatment was not statistically significant (HR = 1.03; 95%CI 0.52-2.06; P = 0.930). However, multivariate Cox regression results suggested that for AR-V7-positive patients, taxane therapy was a protective factor for OS (HR = 0.35; 95%CI 0.20-0.60; P < 0.05). Conclusion: The expression of AR-V7 indicates a poor prognosis and is an independent risk factor for OS in AA/E-treated mCRPC patients. However, AR-V7 positive status does not play the same role in taxane-treated patients. In addition, compared to AA/E, taxane treatment is a protective factor for OS in AR-V7-positive patients. AR-V7 may thus be an effective biomarker for treatment prognosis in patients with mCRPC.
Docetaxel has been proved to provide survival benefit for advanced prostate cancer (PCa) patients. Resistance to docetaxel further reduces the survival of these patients. Herein, we performed a comprehensive bioinformatic analysis to identify differentially expressed genes (DEGs) between docetaxel sensitive and resistant PCa (DRPC) cell based on Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for functional and pathway analysis of DEGs. The STRING database, cytoscape software and plug-in 'cytoHubba' were used to construct protein-protein interaction (PPI) networks and identify hub genes. Survival analysis were performed via GEPIA database. Finally, we conducted immune infiltration analysis by TIMER. A total of 460 DEGs were identified. GO functional analysis showed that these DEGs are mainly enriched in chemotaxis, negative regulation of intracellular signal transduction, and regulation of cell adhesion, positive regulation of inflammatory response, regulation of response to cytokine stimulus. According to the results of KEGG pathway analysis, these DEGs are mainly involved in signaling by Rho GTPases, Miro GTPases and RHOBTB3; interferon Signaling; arginine biosynthesis; PI3K-Akt signaling pathway; cytokine-cytokine receptor interaction; MAPK signaling pathway. Finally, CCNB1 and EZH2 were identified as prognostic hub genes and the expression of these two genes were associated with immune infiltration. The present study may helps to improve the understanding of the molecular mechanisms of DRPC and facilitate the selection of therapeutic and prognostic biomarkers for DRPC.
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