Evaluation of the prognostic value of CBXs in gastric cancer patients

Abstract

Chromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.

Figure 1

mRNA expression of CBXs in GC tissues and adjacent normal tissues (GEPIA). CBX2/3/4/5 mRNA expression was higher in primary GC tissues than in normal tissues (B–E). CBX7 mRNA expression was lower in primary GC tissues than in normal tissues (G). CBX1/6/8 mRNA expression was not significantly different between primary GC tissues and normal tissues (A,F,H). *P ˂ 0.01.

Figure 2

Relationship between the mRNA expression of CBXs and individual cancer stages of GC patients. The mRNA expression levels of 8 CBXs were remarkably related to individual cancer stages, and patients who were in more advanced stages tended to exhibit higher mRNA expression levels of CBXs. The mRNA expression levels of CBX1/3, CBX2/5, and CBX4/6 were the highest in stage 3 (A,C), stage 4 (B,E), and stage 2 (D,F), respectively. However, the mRNA expression levels of CBX7/8 were the highest in stage 1 (G,H). *P ˂ 0.05, **P ˂ 0.01, ***P ˂ 0.001.

Figure 3

Association of the mRNA expression levels of CBXs with tumor grades in GC patients. The mRNA expression levels of 8 CBXs were significantly correlated with tumor grades, and as tumor grade increased, the mRNA expression levels of CBXs increased. The mRNA expression levels of CBX1/2/5/6/7 were the highest in grade 3 tumors (A,B,E–G). However, the mRNA expression levels of CBX3/4/8 were the highest in grade 2 tumors (C,D,H). *P ˂ 0.05, **P ˂ 0.01, ***P ˂ 0.001.

Figure 4

Genetic mutations in CBXs and their association with OS and DFS in GC patients (cBioPortal). The mutation rate of CBXs in GC patients was 37%. CBX3 and CBX8 were the two genes with the most genetic alterations, with mutation rates of 14% and 10%, respectively (A). Genetic mutations in CBXs were not associated with OS (B) or DFS (C) in GC patients. No variables were adjusted.