CBX3 Promotes Gastric Cancer Progression and Affects Factors Related to Immunotherapeutic Responses

Cancer Manag Res. 2020 Oct 14:12:10113-10125. doi: 10.2147/CMAR.S271807. eCollection 2020.

Authors

Hexin Lin^#^{1

2}, Jiabian Lian^#^{3

4}, Lu Xia^#^{4

5}, Guoxian Guan², Jun You^{1

4}

Affiliations

¹ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
² Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
³ Department of Laboratory Medicine, Xiamen Key Laboratory of Genetic Testing, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
⁴ School of Clinical Medicine, Fujian Medical University, Fuzhou, People's Republic of China.
⁵ Laboratory of Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.

^# Contributed equally.

Abstract

Background: Chromobox 3 (CBX3) is a member of the chromobox family proteins, which plays a critical role in tumor progression, but the exact function of CBX3 in gastric cancer remains unknown. The current research mainly investigates the underlying mechanisms and clinical value of CBX3 in gastric cancer.

Methods: Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of CBX3 in gastric cancer. CBX3 expression was further determined by immunohistochemistry (IHC). The function of CBX3 on proliferation, migration and the cell cycle was explored via colony-forming, cell cycle and transwell assays, respectively. Moreover, RNA sequencing (RNA-seq) in AGS cells and two cohorts was utilized to explore the specific mechanism of CBX3.

Results: CBX3 expression was upregulated in human gastric cancer tissues and the expression level was closely associated with adverse signs. Knockdown of CBX3 in gastric cancer cells significantly inhibited the malignant phenotype. In addition, RNA-seq analysis revealed that CBX3 regulates genes related to the cell cycle, mismatch repair and immune-related pathways. Furthermore, the expression of CBX3 was significantly and inversely related to the abundance of tumor-infiltrating lymphocytes (TILs), PDCD1 and PDCD1LG2 expression and immunotherapy responses. Moreover, CBX3 influences the effectiveness of chemotherapy, thereby impacting the prognosis of gastric cancer patients.

Conclusion: CBX3 contributes to gastric cancer progression and is associated with chemotherapy and immunotherapy response. CBX3 may serve as a new diagnostic biomarker and potential target for immunotherapy and chemotherapy in gastric cancer.

Keywords: chemotherapy; chromobox 3; gastric cancer; immunotherapy; survival; tumorigenesis.

Grants and funding

This work was funded by the National Natural Science Foundation of China (Nos. 81802268), Fujian Provincial Department of Science and Technology (Nos. 2018J01381), Fujian Provincial Health Commssion (Nos.2018-2-60) and the Xiamen Municipal Health Commssion (Nos 3502Z20184022).