Hepatocellular carcinoma (Hcc) is one of the most common types of cancer, which is associated with a poor prognosis. it is necessary to identify novel prognostic biomarkers and therapeutic targets to improve the survival of patients with Hcc. in the present study, a seven-gene signature associated with HCC progression was identified using weighted gene co-expression network analysis and least absolute shrinkage and selection operator, and its prognostic prediction value was confirmed in The Cancer Genome Atlas-liver HCC and International Cancer Genome Consortium liver cancer-riKen, Japan cohorts. Subsequently, a rarely reported gene, epoxide hydrolase 2 (ePHX2), was selected for further validation. downregulation of ePHX2 in Hcc was revealed using multiple expression datasets. Furthermore, reduced expression of EPHX2 was confirmed in HCC tissue samples and cell lines using reverse transcription-quantitative polymerase chain reaction and western blotting. additionally, Kaplan-Meier survival curves indicated that patients with higher ePHX2 expression exhibited better prognosis, and clinicopathological analysis also revealed elevated ePHX2 levels in patients with early-stage Hcc. notably, ePHX2 was identified as an independent prognostic biomarker for overall survival of patients with HCC. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis were performed to elucidate the functions of ePHX2. The results suggested that ePHX2 expression was closely associated with metabolic reprogramming. Finally, the prognostic value of ePHX2 was evaluated using Hcc tissue microarrays. in conclusion, downregulation of ePHX2 was significantly associated with the development of HCC; therefore, ePHX2 may be considered a putative therapeutic candidate for the targeted treatment of Hcc.
There are many treatments for metastatic colorectal cancer (mCRC). Among them, uncertainty remains especially concerning the clinical benefit of different regimens for left-sided RAS wild-type (WT) mCRC in the triple-drug therapy era. No studies have been conducted to answer this critical clinical issue. We performed a comprehensive analysis of published data and real-world data. First, we conducted analyses of the published trials to show the landscape of efficacy and safety in the treatments of left-sided RAS WT mCRC. Then, we initiated a multicenter real-world study as the validation dataset. This study included six published randomized controlled trials (RCTs) and a total of 1925 patients. The double-drug regimen plus cetuximab/panitumumab (D + C/P) achieved the longest overall survival (OS) in patients with left-sided mCRC (HR = 0.74, 95%CI: 0.57–0.98), while triple-drug regimen with bevacizumab (T + B, HR = 1.1, 95%CI: 0.63–2.0), compared with double-drug with bevacizumab (D + B). The D + C/P had the highest overall response rate (ORR) in patients with left-sided mCRC (OR = 1.8, 95%CI: 0.89–3.8), while T + B (OR = 1.8, 95%CI: 0.70–4.8), compared with D + B. The multicenter real-world cohort showed the double-drug regimen plus cetuximab had longer progression-free survival (PFS) in left-sided mCRC patients than the triple-drug regimen with bevacizumab. The safety analysis showed the incidence of the adverse events (grade≥3) in the triple-drug therapy plus bevacizumab was higher than that in the double-drug therapy plus cetuximab/panitumumab. This work demonstrates the ranking of three regimens for therapeutic efficacy and safety in patients with left-sided RAS WT mCRC. The double-drug regimen plus cetuximab/panitumumab appears more effective and safer than double-drug and triple-drug based regimens with bevacizumab. Further trials and cohort analyses on this topic would increase confidence in these results.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.