CCT6A and CHCHD2 Are Coamplified with EGFR and Associated with the Unfavorable Clinical Outcomes of Lung Adenocarcinoma

Abstract

Chaperonin containing TCP1 subunit 6A (CCT6A) and coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) are located at the chromosome 7p11 region proximal to epidermal growth factor receptor (EGFR). However, the amplifications, expressions, and the prognostic effects of CCT6A and CHCDH2 in lung adenocarcinoma (LUAD) are unclear. Here, using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we found that CCT6A was coamplified and coexpressed with EGFR in LUAD patients. CCT6A amplification was correlated with the unfavorable outcomes of LUAD. Moreover, CCT6A was upregulated in LUAD tissues, and CCT6A overexpression was correlated with the unfavorable relapse free survival or overall survival of LUAD. On the contrary, CCT6A was hypomethylated in LUAD, and CCT6A hypermethylation was correlated with the favorable overall survival of LUAD. Similar expression and methylation profiling of CCT6A were obtained in 479 lung normal tissues and 544 LUAD tissues collected from 11 independent datasets. In 1,462 LUAD patients from eight independent cohorts, CCT6A was also correlated with LUAD relapse-free survival or overall survival. Furthermore, CCT6A overexpression promoted the cell growth and invasion of LUAD. Identification of genes differentially expressed in CCT6A highly expressed LUAD patients revealed that CHCHD2 was the most correlated with CCT6A expression. CHCHD2 was coamplified with CCT6A. CHCHD2 was upregulated in LUAD tissues, and overexpression of CHCHD2 was correlated with the shorted relapse-free survival or overall survival of LUAD. Overall, our results revealed that CCT6A and CHCHD2 were coamplifying and coexpressing with EGFR and were correlated with the unfavorable clinical outcomes of LUAD.