KLHL21, a novel gene that contributes to the progression of hepatocellular carcinoma. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Shi, Lei; Zhang, Wenfa; Zou, Fagui; Mei, Lihua; Wu, Gang; Teng, Yong
• Is Part Of: BMC cancer. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: KLHL21 -- Bioinformatics -- HCC -- Biomarker; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-016-2851-7
• Languages: English
• ISSNs: 1471-2407

Abstract

Abstract Background Hepatocellular carcinoma (HCC) has very high prevalence and associated-mortality. However, targeted therapies that are currently used in clinical practice for HCC have certain limitations, in part because of the lack of reliable and clinically applicable biomarkers that can be used for diagnosis and prognosis assessments and for the surveillance of treatment effectiveness. Methods Meta-analysis was used to analyze the integrated microarray data for global identification of a set of robust biomarkers for HCC. Quantitative RT-PCR (qRT-PCR) was performed to validate the expression levels of selected genes. Gene expression was inhibited by siRNA. CellTiter 96® AQueous One Solution Cell Proliferation assays were used to determine cell proliferation, and Transwell assays were used to determine cell migration and invasion potential. Results Meta-analysis of the expression data provided a gene expression signature from a total of 1525 patients with HCC, showing 1529 up-regulated genes and 478 down-regulated genes in cancer samples. The expression levels of genes having strong clinical significance were validated by qRT-PCR using primary HCC tissues and the paired adjacent noncancerous liver tissues. Up-regulation ofVPS45, WIPI1, TTC1, IGBP1 andKLHL21 genes and down-regulation ofFCGRT gene were confirmed in clinical HCC samples.KLHL21 was the most promising gene for potential use as a bioclinical marker in this analysis. Abrogating expression of it significantly inhibited cell proliferation, migration and invasion. Conclusions Our study suggests thatKLHL21 is a potential target for therapeutic intervention. Our findings also provide novel candidate genes on a genome-wide scale, which may have significant impact on the design and execution of effective therapy of HCC patients.