Overexpression of CHAF1A is associated with poor prognosis, tumor immunosuppressive microenvironment and treatment resistance

Xia Sun; Qiushuang Ma; Yahong Cheng; Huangwei Huang; Jing Qin; Mengchen Zhang; Sifeng Qu

doi:10.3389/fgene.2023.1108004

Overexpression of CHAF1A is associated with poor prognosis, tumor immunosuppressive microenvironment and treatment resistance

Front Genet. 2023 Mar 9:14:1108004. doi: 10.3389/fgene.2023.1108004. eCollection 2023.

Authors

Xia Sun¹, Qiushuang Ma¹, Yahong Cheng¹, Huangwei Huang^{2

3}, Jing Qin⁴, Mengchen Zhang¹, Sifeng Qu^{2

3}

Affiliations

¹ Department of Pharmacology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
² Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
³ Department of Urology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
⁴ Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Abstract

Background: As distinct marker of proliferating cells, chromatin assembly factor-1 (CAF-1) was critical in DNA replication. However, there is paucity information about the clinical significance, functions and co-expressed gene network of CHAF1A, the major subunit in CAF-1, in cancer. Methods: Bioinformatic analysis of CHAF1A and its co-expression gene network were performed using various public databases. Functional validation of CHAF1A was applied in breast cancer. Results: Overexpression of CHAF1A was found in 20 types of cancer tissues. Elevated expression of CHAF1A was positively correlated with breast cancer progression and poor patients' outcome. The analysis of co-expression gene network demonstrated CHAF1A was associated with not only cell proliferation, DNA repair, apoptosis, but cancer metabolism, immune system, and drug resistance. More importantly, higher expression of CHAF1A was positively correlated with immunosuppressive microenvironment and resistance to endocrine therapy and chemotherapy. Elevated expression of CHAF1A was confirmed in breast cancer tissues. Silencing of CHAF1A can significantly inhibit cell proliferation in MDA-MB-231 cells. Conclusion: The current work suggested that overexpression of CHAF1A can be used as diagnostic and poor prognostic biomarker of breast cancer. Higher expression of CHAF1A induced fast resistance to endocrine therapy and chemotherapy, it may be a promising therapeutic target and a biomarker to predict the sensitivity of immunotherapy in breast cancer.

Keywords: CHAF1A; cancer; immune; metabolism; prognosis.

Grants and funding

This project was supported by the National Natural Science Foundation, China (81872894), Joint Fund of Shandong Provincial Natural Science Foundation (ZR2021LSW026), Guangdong Basic and Applied Basic Research Foundation (2021A1515220181), China Postdoctoral Science Foundation (2020M672066), Shandong Provincial Natural Science Foundation (ZR2020MH264), Beijing Bethune Charitable Foundation (mnzl202016), Shandong Province Postdoctoral Innovation Project (202002010), CSCO-Pilot Cancer Research Foundation (Y-2019AZQN-0039).