Identification of the Roles of Chromobox Family Members in Gastric Cancer: A Study Based on Multiple Datasets

Abstract

Background: As the important components in polycomb repressive complexes 1 (PRC1) and heterochromatin protein 1 (HP1), Chromobox (CBX) family members are involved in epigenetic regulatory function, transcriptional repression, and other cellular metabolisms. Increasing studies have indicated significant associations between CBX and tumorigenesis, which is a progression in different types of cancers. However, the information about the roles of each CBX in gastric cancer is extremely limited.

Methods: We explored CBX mRNA expression, corrections with clinicopathological parameters, protein expression, prognostic values, enrichment analysis with several databases including Oncomine, Human Protein Atlas, UALCAN, Kaplan-Meier plotter, cBioPortal, GeneMANIA, and Enrichr.

Results: In our study, comparing to the normal tissues, higher mRNA expression of CBX1/2/3/4/5/8 and lower mRNA expression of CBX7 were found in GC tissues while upregulations of CBX1/2/3/4/5/8 and downregulations of CBX7 were indicated to be significantly correlated to the nodal metastasis status and individual cancer stages in GC patients. As for protein level, the expression of CBX2/3/4/5/6 was higher and the expression of CBX7 was lower in the GC tissues than those in the normal. What is more, higher mRNA expression of CBX1/5/6/8 and lower mRNA expression of CBX7 were markedly correlated to poor outcomes of OS and FP in GC patients. Besides, high mutation rate of CBXs (42%) was observed in GC patients.

Conclusions: We suggest that CBX5/7 may serve as potential therapeutic targets for GC while CBX1/8 may serve as potential prognostic indicators for GC.

Figure 1

Transcriptional levels of the CBX family members in different cancers (Oncomine, P value: 0.001 and fold − change : 1.5).

Figure 2

mRNA and protein expression of CBXs (UALCAN and Human Protein Atlas): (a) mRNA expression of different CBXs in STAD and normal tissues (UALCAN, ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001); (b) protein expression of different CBXs in GC and the normal tissues (Human Protein Atlas).

Figure 3

Clinicopathological parameters and CBX mRNA levels in STAD patients (UALCAN): (a) correlation between the expression level of CBXs and nodal metastatic status in STAD patients (UALCAN, ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001); (b) correlation between expression of CBXs and individual cancer stage in STAD patients (UALCAN, ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001).

Figure 4

Prognostic value of mRNA level of CBX family members in GC patients (Kaplan-Meier plotter, P < 0.05 was considered statistically significant).

Figure 5

Genetic alterations, interactions, and enrichment analysis of CBXs in GC: (a) summary of CBX alteration in STAD; (b) alterations in CBXs in GC; (c) correction of CBXs with each other (cBioPortal); (d) interaction analysis of CBXs (GeneMANIA). Summary of alterations in CBXs in HCC: (e) GO enrichment analysis; (f) Reactome pathway prediction. BP: biological processes; CC: cellular components; MF: molecular functions.