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.

Genome skimming-based simple sequence repeat (SSR) marker discovery and characterization in Grevillea robusta

“…Here, the functional enrichment analysis of the genes were done through g:Profiler, where the results characterized into GO ID and p-value with highest involved in the biological process (337), followed by cellular component (99) and molecular function (67). Recently, this kind of characterization and annotation of genes were used to predict therapeutic drugs against COVID-19 (Tan et al 2021 ), validation of immune genes (Karthikeyan et al 2021 ), identification of novel prognostic biomarker (Xu et al 2020 ), and analyses of Integrated Gene Expression Profiling Data (IGEPA) (You et al 2020 ).…”

CELSR2 deficiency suppresses lipid accumulation in hepatocyte by impairing the UPR and elevating ROS level

“…The cell viability assay showed that CELSR2 knockdown significantly decreased cell survival (Figure 5A), which is consistent with a previous study. 9 Moreover, CELSR2 loss significantly reduced the cell colony formation (Figure 5B,C). Besides, we detected significantly decreased cell proliferation in the CELSR2 knockdown group by using the EdU incorporation assay (Figure 5D,E).…”

“…CELSR2 is a member of the three atypical cadherins, located at the plasma membrane by seven transmembrane domains, which are structurally characterized by nine N‐terminal cadherin repeats in the large ectodomain 8 . CELSR2 mRNA is mainly found in the nervous system, also expressed in skin, reproductive systems, kidneys, gastrointestinal, and muscle tissues 8,9 . CELSR2 has been widely reported in ciliogenesis and neural development, which is conserved from Drosophila to mammals 10 .…”

“…12 Besides, current studies showed that the CELSR2 gene is related to many human diseases, including coronary artery disease, 4 idiopathic scoliosis, 17 mammary and endometrial carcinogenesis, 18 and hepatocellular carcinoma. 9 Additionally, SORT1 encoded by the cardiovascular risk locus 1p13. 3, is an intracellular sorting receptor for apoB100, which facilitates the formation and hepatic export of lipoprotein.…”

Expression and Gene Regulation Network of GRK6 in Clear Cell Renal Cell Carcinoma based on Comprehensive Bioinformatics Analysis

“…Our research is based on the most prevalent bioinformatics theory and uses online tools to analyze target genes from tumor data from public databases. Meanwhile, this method has the advantages of low cost, large sample size and simplicity compared with traditional chip screening [54]. This enables large-scale ccRCC genomics research and subsequent functional studies.…”