CGB5 expression is independently associated with poor overall survival and recurrence-free survival in patients with advanced gastric cancer

Abstract

The human CGB5 gene encodes chorionic gonadotropin (hCG)β 5, which is aberrantly expressed in trophoblastic neoplasm and in some non-trophoblastic neoplasms. Fucntional studies observed that it involved tumor initiation, growth, and metastatic outgrowth. In this study, using data from the International Cancer Genome Consortium (ICGC) and the Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD), we assessed the independent prognostic value of CGB5 expression in patients with primary gastric cancer (GC). Results showed that CGB5 expression was nearly not expressed in normal GC tissues. In comparison, its expression was detected in 214 of the 415 primary GC cases (51.6%) in TCGA-STAD and was associated with poor response to primary therapy and a higher risk of recurrence and death. In early stages, CGB5 expression was not a prognostic factor in terms of OS (HR: 1.448; 95% CI: 0.811-2.588, P = 0.211) or RFS (HR: 1.659; 95% CI: 0.778-3.540, P = 0.190). However, its expression was independently associated with unfavorable OS (HR: 1.719; 95% CI: 1.115-2.651, P = 0.014) and RFS (HR: 3.602; 95% CI: 1.708-7.598, P = 0.001) in advanced stages. Using deep sequencing data from TCGA-STAD, we found that CGB5 expression was not related to its genetic amplification or DNA methylation in GC. Based on these findings, we infer that CGB5 expression is common in GC patients and its expression might independently predict poor OS and RFS in advanced stages, but not in early stages of GC.

Keywords: CGB5; hCG β; gastric cancer; overall survival; recurrence-free survival.

Figure 1

Comparison of CGB5 expression in different patient groups. (A) Comparison of CGB5 expression between GC cancer (N = 415) and normal gastric tissues (N = 35). (B) The expression profile of CGB5 in 415 patients. (C) CGB5 protein expression summary in normal human tissues. Data were obtained from: http://www.proteinatlas.org/ENSG00000189052-CGB5/tissue. (D) Representative images of CGB5 IHC staining in normal gastric tissues. (E). CGB5 protein expression summary in some human cancer. Data were obtained from: http://www.proteinatlas.org/ENSG00000189052-CGB5/pathology.

Figure 2

Comparison of CGB5 expression in different GC patient groups. (A–C) Comparison of CGB5 expression between female and male patients (A), in different pathological stages (B) and in patients with responses (CR+PR) and without responses (SD+PD) (C).

Figure 3

Kaplan–Meier curves of OS in GC patients. (A–B) Kaplan–Meier curves of OS in GC patients. Survival curves were generated using data from ICGC (A) and TCGA (B). Patients were divided into CGB5‐positive (>0) and negative (=0) groups.

Figure 4

Kaplan–Meier curves of OS in early and advanced stages of GC patients. (A–B) Kaplan–Meier curves of OS in early stages group (I/II) (A) or in advanced stages group (III/IV) (B). Data were generated using data from TCGA‐STAD. Patients were divided into CGB5‐positive (>0) and negative (=0) groups.

Figure 5

Kaplan–Meier curves of RFS in GC patients. (A–C) Kaplan–Meier curves of RFS in all patients (A), in early stages group (I/II) (B) and advanced stages group (III/IV) (C). Data were generated using data from TCGA‐STAD. Patients were divided into CGB5‐positive (>0) and negative (=0) groups.

Figure 6

The association between CGB5 expression and its DNA amplification and methylation. (A–B) Heatmap (A) and plots chart (B) of CGB5 expression in groups with different genetic alterations. −1: heterozygous loss, 0: copy‐neutral, +1: low‐level copy gain, and +2: high‐level amplification. Heatmap (C) and regression analysis (D) of the correlation between CGB5 DNA methylation and its RNA expression.