Enhanced expression of GABRD predicts poor prognosis in patients with colon adenocarcinoma

Moxin Wu; Keun Young Kim; Won Cheol Park; Han-Seung Ryu; Suck Chei Choi; Min Seob Kim; Ji Yeon Myung; Hyun Seok Choi; Eui Joong Kim; Moon Young Lee

doi:10.1016/j.tranon.2020.100861

Enhanced expression of GABRD predicts poor prognosis in patients with colon adenocarcinoma

Transl Oncol. 2020 Dec;13(12):100861. doi: 10.1016/j.tranon.2020.100861. Epub 2020 Sep 3.

Authors

Affiliations

¹ Department of Medical Laboratory, Affiliated Hospital of Jiujiang University, Jiujiang 332000, China; Department of Physiology, School of Medicine, Wonkwang University, Wonkwang Digestive Disease Research Institute & Institute of Wonkwang Medical Science, Iksan 54538, Republic of Korea.
² Department of General Surgery, Wonkwang University, School of Medicine, Wonkwang Digestive Disease Research Institute, Iksan 54538, Republic of Korea.
³ Department of Gastroenterology, Wonkwang University, School of Medicine, Wonkwang Digestive Disease Research Institute, Iksan 54538, Republic of Korea.
⁴ Department of Physiology, School of Medicine, Wonkwang University, Wonkwang Digestive Disease Research Institute & Institute of Wonkwang Medical Science, Iksan 54538, Republic of Korea.
⁵ Department of Physiology, School of Medicine, Wonkwang University, Wonkwang Digestive Disease Research Institute & Institute of Wonkwang Medical Science, Iksan 54538, Republic of Korea. Electronic address: lmy6774@wku.ac.kr.

Abstract

Neurotransmitters are reported to be involved in tumor initiation and progression. This study aimed to elucidate the prognostic value of γ-aminobutyric acid type A receptor δ subunit (GABRD) in colon adenocarcinoma (COAD) using the data from The Cancer Genome Atlas (TCGA) database. The GABRD mRNA expression levels in the COAD and normal tissues were compared using the Wilcoxon rank-sum test. The correlation between clinicopathologic characteristics and GABRD expression was analyzed by Wilcoxon rank-sum test or Kruskal-Wallis test and logistic regression. The prognostic value of GABRD mRNA expression in patients with COAD was determined using the Kaplan-Meier curve and Cox regression analysis. Finally, the molecular mechanisms of GABRD in COAD were predicted by gene set enrichment analysis (GSEA). The COAD tissues exhibited higher GABRD mRNA expression levels than the normal tissues. The logistic regression analysis revealed that GABRD mRNA expression was correlated with TNM stage, N stage, M stage, and microsatellite instability (MSI) status. The Kaplan-Meier survival curve and log-rank test revealed that patients with COAD exhibiting high GABRD mRNA expression were associated with poor overall survival (OS). The multivariate analysis indicated that increased GABRD mRNA expression was an independent prognostic factor and was correlated with a poor OS. The GSEA revealed that GABRD was involved in signaling pathways, including cell adhesion molecules, gap junction, melanogenesis, and mTOR signaling pathway, as well as the signaling pathways associated with basal cell carcinoma or bladder cancer development. In summary, enhanced GABRD mRNA expression may be a potential independent prognostic biomarker for COAD.