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

Background: Polycomb chromobox 4 (CBX4) is a component of the polycomb complex and also a small ubiquitin-related modi-fier 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 immunohistochem-istry 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 (DeoxyriboNu-cleic 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.