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Identification of CELSR2 as a novel prognostic biomarker for hepatocellular carcinoma.

ABSTRACT: BACKGROUND:CELSR2 is postulated to be a receptor involved in contact-mediated communication; however, the specific function of this particular member has not been determined in hepatocellular carcinoma (HCC). METHODS:Here, we explored the expression and function of CELSR2 in HCC patients through data mining and examined the results using clinical samples and in vitro experiments. RESULTS:It was found that CELSR2 mRNA and protein expression levels were significantly higher in cancerous tissue than in normal tissue. The increased mRNA expression of CELSR2 was significantly associated with overall survival (OS) in HCC patients. Moreover, the genetic alteration rate of CELSR2 gene in HCC can reach 8%, and these alterations would deeply influence its neighboring genes, then jointly affecting the occurrence and development of tumor through cell adhesion and numerous common carcinogenic pathways. Our in vitro results indicated that the depletion of CELSR2 inhibited liver cancer cell proliferation and invasion. Univariate and multivariate Cox regression analyses showed that CELSR2 could be viewed as an independent risk factor for HCC patients. CONCLUSIONS:This study demonstrated that data mining could efficiently reveal the roles of CELSR2 in HCC and its potential regulatory networks. The CELSR2 protein level may serve as a novel prognostic biomarker for HCC.

SUBMITTER: Xu M

PROVIDER: S-EPMC7161135 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Identification of CELSR2 as a novel prognostic biomarker for hepatocellular carcinoma.

Xu Mingxing M Zhu Shu S Xu Ruiyun R Lin Nan N

BMC cancer 20200415 1

<h4>Background</h4>CELSR2 is postulated to be a receptor involved in contact-mediated communication; however, the specific function of this particular member has not been determined in hepatocellular carcinoma (HCC).<h4>Methods</h4>Here, we explored the expression and function of CELSR2 in HCC patients through data mining and examined the results using clinical samples and in vitro experiments.<h4>Results</h4>It was found that CELSR2 mRNA and protein expression levels were significantly higher i ...[more]

PMID: 32293343

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Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown.MethodsTCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan-Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro.ResultsMRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro.ConclusionsWe demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.

Dataset Information

Identification of CELSR2 as a novel prognostic biomarker for hepatocellular carcinoma.

Publications

Identification of CELSR2 as a novel prognostic biomarker for hepatocellular carcinoma.

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