High Expression of Polycomb Chromobox 4 in Stomach Adenocarcinoma Promotes Chemotherapy Resistance

Abstract

Background: Polycomb chromobox 4 (CBX4) is a component of the polycomb complex and also a small ubiquitin-related modifier E3 ligase. CBX4 has been identified as a poor prognostic marker for various cancers, but its role in stomach adenocarcinoma (STAD) chemotherapy resistance remains unclear. Purpose: The aim of this study was to study the expression of CBX4 in STAD and its role in STAD chemotherapy resistance. Method: This study looked for CBX4 expression level in patients with STAD and adjacent normal tissues by immunohistochemistry generated CBX4 knockout (KO) STAD cell line with CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 technology, checked for CBX4-related transcriptional profile with RNA (Ribonucleic Acid)-seq technology and measured chemotherapy resistance with CCK8 (Cell Counting Kit-8) assay. Result: In this study, CBX4 was found to be highly expressed in STAD tumor tissues. CBX4-related transcriptional profile was illustrated in CBX4 KO STAD cell lines, showing that CBX4 regulated the alternative splicing involved in DNA (DeoxyriboNucleic Acid)-repair pathways. CBX4 KO STAD cells were found to be more vulnerable to 5-fluorouracil (5-FU) treatment. Conclusions: This study confirmed the high expression of CBX4 level in STAD tissues and revealed that CBX4 is a potential biomarker for predicting 5-FU sensitivity in STAD. Inhibition of CBX4 is a potential strategy to overcome the drug resistance of 5-FU in STAD treatment.