Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Novel biomarkers of ccRCC may provide crucial information on tumor features and prognosis. The present study aimed to determine whether the expression of γ-aminobutyric acid (GABA) A receptor subunit θ (GABRQ) could serve as a novel prognostic marker of ccRCC. GABA is the main inhibitory neurotransmitter in the brain that activates the receptor GABAA, which is comprised of three subunit isoforms: GABRA3, GABRB3 and GABRQ. A recent study reported that GABRQ is involved in the initiation and progression of hepatocellular carcinoma; however, the role of GABRQ in ccRCC remains unknown. In the present study, clinical and transcriptomic data were obtained from cohorts of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Differential GABRQ expression levels among early (TI and II), late (TIII and IV), nonmetastatic (M0) and metastatic (M1, primary tumor) stages of ccRCC samples were then identified. Furthermore, the use of GABRQ as a prognostic gene was analyzed using Uno's C-index based on the time-dependent area under the curve (AUC), the AUC of the receiver operating characteristic curve at 5 years, the Kaplan-Meier survival curve and multivariate analysis. The survival curve analysis revealed that low GABRQ mRNA expression was significantly associated with a poor prognosis of ccRCC (P<0.001 and P=0.0012 for TCGA and ICGC data, respectively). In addition, analyses of the C-index and AUC values further supported this discriminatory power. Furthermore, the prognostic value of GABRQ mRNA expression was confirmed by multivariate Cox regression analysis. Taken together, these results suggested that GABRQ mRNA expression may be considered as a novel prognostic biomarker of ccRCC.
Oncology letters. 2019 Oct 04 [Epub]
Dongjun Lee, Mihyang Ha, Chae Mi Hong, Jayoung Kim, Su Min Park, Dongsu Park, Dong Hyun Sohn, Ho Jin Shin, Hak-Sun Yu, Chi Dae Kim, Chi-Dug Kang, Myoung-Eun Han, Sae-Ock Oh, Yun Hak Kim
Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 50612, Republic of Korea., Department of Anatomy, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 50612, Republic of Korea., Department of Molecular Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 50612, Republic of Korea., Department of Hematology-Oncology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 50612, Republic of Korea., Department of Parasitology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 50612, Republic of Korea., Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.