Background Although genes have been previously detected in pancreatic cancer (PC), aberrant genes that play roles in resectable pancreatic cancer should be further assessed. Methods Messenger RNA samples and clinicopathological data corrected with PC were downloaded from The Cancer Genome Atlas (TCGA). Resectable PC patients were randomly divided into a primary set and a validation set. Univariable Cox regression analysis, lasso-penalized Cox regression analysis, and multivariable Cox analysis were implemented to distinguish survival-related genes (SRGs). A risk score based on the SRGs was calculated by univariable Cox regression analysis. A genomic-clinical nomogram was established by integrating the risk score and clinicopathological data to predict overall survival (OS) in resectable PC. Results Five survival-related genes (AADAC, DEF8, HIST1H1C, MET, and CHFR) were significantly correlated with OS in resectable PC. The resectable PC patients, based on risk score, were sorted into a high-risk group that showed considerably unfavorable OS (p < 0.001) than the low-risk group, in both the primary set and the validation set. The concordance index (C-index) was calculated to evaluate the predictive performance of the nomogram were respectively in the primary set [0.696 (0.608–0.784)] and the validation set [0.682 (0.606–0.758)]. Additionally, gene set enrichment Analysis discovered several meaningful enriched pathways. Conclusion Our study identified five prognostic gene biomarkers for OS prediction and which facilitate postoperative molecular target therapy for the resectable PC, especially the nomic-clinical nomogram which may be used as an effective model for the postoperative OS evaluation and also an optimal therapeutic tool for the resectable PC.
BackgroundBladder carcinoma (BLCA) is a heterogeneous disease that makes it difficult to achieve proper individual treatment and predict prognosis. This study aimed to develop a risk score from a new perspective of pyroptosis and guide accurate treatment and prognosis prediction for BLCA.MethodsThe TCGA-BLCA cohort data were downloaded from The Cancer Genome Atlas database. Two external validation cohorts were collected from the Gene Expression Omnibus. Another independent validation cohort (the Xiangya cohort) was recruited from our hospital. The least absolute shrinkage and selector operation (LASSO) algorithm and Cox regression models were used to establish the pyroptosis risk score. Thereafter, we correlated the pyroptosis risk score with prognosis, tumor microenvironment (TME) immune hallmarks, and multiple treatments, including anticancer immunotherapy, chemotherapy, radiotherapy, and targeted therapy.ResultsThe pyroptosis risk score was an independent prognostic predictor of BLCA. We found that the activities of multiple steps of the anticancer immune response cycle, such as the release of cancer cell antigens, CD8 T cell recruitment, and NK cell recruitment, were significantly higher in the high-risk score group than in the low-risk score group. In addition, the infiltration levels of the corresponding tumor-infiltrating immune cells (TIICs), such as CD8 T cells and NK cells, were positively correlated with the pyroptosis risk score. Thus, BLCA with a high-risk score may be associated with inflamed phenotypes. Simultaneously, the expression of multiple immune checkpoints (such as PD-L1, CTLA-4, and PD-1) and enrichment scores of gene signatures positively correlated with immunotherapy response were positively correlated with the pyroptosis risk score. Therefore, patients with a high pyroptosis risk score may be more sensitive to immunotherapy. In addition, patients with high pyroptosis risk scores may be more sensitive to chemotherapeutic drugs, such as cisplatin, docetaxel, and paclitaxel. In addition, the pyroptosis risk score accurately predicted the molecular subtypes of BLCA, which were cross-validated in several independent systems.ConclusionsThis study developed and validated a robust pyroptosis risk score that can predict the clinical outcomes and TME immune phenotypes of BLCA. In summary, the pyroptosis risk score helps drive precision therapy in patients with BLCA.
BackgroundThe prognostic nutrition index (PNI), which has been evaluated in various kinds of cancers, offered a simple yet effective approach to predict the prognosis. The aim of this meta-analysis is to reveal the correlation between preoperative PNI and the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) who underwent curative resection.MethodsWe searched the PubMed, Embase, Web of Science and Cochrane Library databases, and extracted the hazard ratio (HR) with 95% confidential interval (CI) from eligible studies. The pooled HR with 95% CI was applied to evaluate the association between PNI and overall survival (OS), recurrence-free survival (RFS).ResultsA total of fourteen studies with 3,385 patients were included for meta-analysis. The results (the pooled HR: 1.664, 95% CI: 1.424–1.994, I² = 42.6%, p value = 0.046) indicated that low preoperative PNI was closely related to poor OS. In addition, the results suggested that PNI was negatively correlated with RFS (the pooled HR: 1.369, 95%CI: 1.080–1.734). The robustness of these pooled results was verified by our subgroup analysis and sensitivity analysis. Moreover, different cutoff values among studies are responsible for the heterogeneity of pooled HR of OS through meta-regression analysis (p value = 0.042). Funnel plots, Begg's test (p value = 0.228) and Egger’s test (p value = 0.702) indicated no significant publication bias in OS.ConclusionPreoperative PNI might be a promising marker to predict the prognosis of PDAC patients who underwent curative resection.
Background: Comparison between endosonographic ultrasonography (EUS)-guided celiac ganglia neurolysis (CGN) and EUSguided celiac plexus neurolysis (CPN) in pain management for pancreatic cancer has engendered controversy. To analyze the effectiveness and safety of EUS-CGN and figure out whether EUS-CGN is better than EUS-CPN, a qualitative systematic review was conducted.Methods: Studies were searched from Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE up to April 2020. We only included studies with full-text and in English and assessed study quality with Newcastle-Ottawa Scale or Cochrane risk-ofbias tool. We recorded details of study design, participants, procedure performed, protocol of follow-up, pain response, quality of life, survival, and adverse events. The study was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement 2009.Results: Five studies involving 319 patients were included. Short-term pain response rates ranged from 65.0% to 88.46% in EUS-CGN group and most studies reported its superiority over EUS-CPN. As for adverse events, the incidence of transient hypotension and gastrointestinal symptoms seemed comparable, while results of initial pain exacerbation varied among studies. Besides, EUS-CGN might provide a shorter survival.Conclusion: EUS-CGN can be safely performed while it may shorten survival. In terms of short-term pain response, EUS-CGN is better than EUS-CPN while no conclusion of long-term pain control can be drawn.Abbreviations: CGN = celiac ganglia neurolysis, CPN = celiac plexus neurolysis, EUS = endosonographic ultrasonography, RCT = randomized controlled trial, RFA = radiofrequency ablation, VAS = visual analog scale.
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