ABSTRACT
BACKGROUND: Accumulating evidence has revealed that several long non-coding ribonucleic acids (lncRNAs) are crucial in the progress of hepatocellular carcinoma (HCC). AIM: To classify a long non-coding RNA, i.e., lncRNA W5, and to determine the clinical significance and potential roles of lncRNA W5 in HCC. METHODS: The results showed that lncRNA W5 expression was significantly downregulated in HCC cell lines and tissues. Analysis of the association between lncRNA W5 expression levels and clinicopathological features suggested that low lncRNA W5 expression was related to large tumor size (P < 0.01), poor histological grade (P < 0.05) and serious portal vein tumor thrombosis (P < 0.05). Furthermore, Kaplan-Meier survival analysis showed that low expression of lncRNA W5 predicts poor overall survival (P = 0.016). RESULTS: Gain-of-loss function experiments, including cell counting kit8 assays, colony formation assays, and transwell assays, were performed in vitro to investigate the biological roles of lncRNA W5. In vitro experiments showed that ectopic overexpression of lncRNA W5 suppressed HCC cell proliferation, migration and invasion; conversely, silencing of lncRNA W5 promoted cell proliferation, migration and invasion. In addition, acting as a tumor suppressor gene in HCC, lncRNA W5 inhibited the growth of HCC xenograft tumors in vivo. CONCLUSION: These results showed that lncRNA W5 is down-regulated in HCC, and it may suppress HCC progression and predict poor clinical outcomes in patients with HCC. LncRNA W5 may serve as a potential HCC prognostic biomarker in addition to a therapeutic target.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Prognosis , RNA, Long Noncoding/geneticsABSTRACT
PURPOSE: Understanding how sex impacts the efficacy of anticancer agents is a crucial step toward personalized and precision medicine. This review and meta-analysis evaluated sex differences in hazard ratios (HRs) of progression-free survival and overall survival in representative Phase III clinical trials of non-small-cell lung cancer (NSCLC). METHODS: Data were extracted from 24 large-scale clinical trials that included 12,000 male and 7000 female patients. The data were examined for HR differences between subgroups by sex, smoking status, and age, and for potential sex-smoking status, sex-age, and sex-drug interactions, during cancer treatment. FINDINGS: Summarized information revealed variations in the influences of sex, smoking status, and age on the efficacy of drugs used for the treatment of NSCLC. The male and female subgroups had different HR values. Smoking status, age, and the percentage of female patients in a treatment group had no influence on the sex HR. The sex difference was supported by a set of data collected from all journals. IMPLICATIONS: The findings from this meta-analysis are important for assessing potential toxicity during drug treatment in both sexes. The outcomes measures of a drug in clinical application should be specified by subpopulation, such as males versus females, as a first step in personalized medicine.