GABRD promotes progression and predicts poor prognosis in colorectal cancer

Abstract

Little is known about the functional roles of gamma-aminobutyric acid type A receptor subunit delta (GABRD) in colorectal cancer (CRC). The expression of GABRD between CRCs and adjacent normal tissues (NTs), metastasis and primary tumors was compared using public transcriptomic datasets. A tissue microarray and immunohistochemical staining (IHC) were used to determine the clinical and prognostic significance of the GABRD in CRC. We used gain-of-function and loss-of-function experiments to investigate the in vitro roles of GABRD in cultured CRC cells. We characterized the potential mechanism of GABRD’s activities in CRC using a Gene Set Enrichment Analysis (GSEA) with The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset. We found that the GABRD expression was significantly increased in CRCs compared to that in NTs, but was similar between metastasis and primary tumors. Overexpression of GABRD was significantly associated with later pTNM stages and unfavorable patient survival. Overexpression of GABRD accelerated while knock-down of GABRD inhibited cell growth and migration. Mechanistically, the function of GABRD might be ascribed to its influence on major oncogenic events such as epithelial–mesenchymal transition (EMT), angiogenesis, and hedgehog signaling. Collectively, GABRD could be a novel prognostic predictor for CRC that deserves further investigation.

Clinical Data and Biocalculation Methods of GABRD Determine the Clinical Characteristics and Immune Relevance of Colorectal Cancer

“…In addition, GABRD gene may be a prognostic marker in gliomas with low expression, and it is associated with poor prognosis [ 10 , 11 ]. In another study, GABRD expression was found to be significantly lower in IDH wild-type diffuse gliomas compared to IDH mutant tumors [ 12 ], and patients with high GABRD expression had a better prognosis than those with low GABRD expression [ 13 ]. Taken together, it is suggested that the functional mechanism of GABRD in cancer needs to be investigated on specific cancer types.…”

A pair of long intergenic non-coding RNA LINC00887 variants act antagonistically to control Carbonic Anhydrase IX transcription upon hypoxia in tongue squamous carcinoma progression

“…1C). All of these genes have been shown to play important roles in tumor progression [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. Interestingly, 8 of these 17 genes have been identified as hypoxia-associated genes, including CA9, gamma-glutamyltransferase 6 (GGT6), KISS1 receptor (KISS1R), enolase 2 (ENO2), hypoxia-inducible lipid droplet-associated protein (HILPDA), EGL-9 family hypoxia inducible factor 3 (EGLN3), endothelial cell specific molecule 1 (ESM1), and NDUFA4 mitochondrial complex-associated like 2 (NDUFA4L2) (Fig.…”

The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma

“…KCNMA1 has been used as a prognosis-related biomarker in several tumors and is strongly correlated with tumor metastasis and calcium channels ( Khaitan et al, 2009 ; Zhang and Yan 2014 ; Wang et al, 2018 ). GABRD is widely reported to be closely associated with colon cancer ( Niu et al, 2020 ; Wu et al, 2020 ). KCNJ15 has been closely related to potassium channels and identified as a molecular marker by investigators in ccRCC ( Liu et al, 2019 ; Zhang J. et al, 2021 ).…”