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

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.

An oncogene regulating chromatin favors response to immunotherapy

“… 45 , 46 Furthermore, both mRNA and protein expression of CHAF1A can predict ICI efficacy, but the optimal detection methods and standards still need to be established. Finally, an inconsistent prognostic role of CHAF1A has been previously reported in GC and other tumors, 16 , 29 , 38 although multiple pieces of evidence for its favorable role in prognosis from several cohorts were provided in this study.…”

“…It would be interesting to find an unexpected dual role for CHAF1A in tumorigenesis and anti-tumor immunoreaction. Previously, CHAF1A was found to be oncogenic and growth-promoting in many tumors, such as colon cancer, 29 neuroblastoma, 30 breast cancer, 38 and GC. 16 In this study, CHAF1A knockdown still inhibited tumor growth in vivo , but it impaired the effect of anti-PD-1 antibody to reduce tumor size and prolong the survival of tumor-carrying mice.…”

Novel DNA damage repair signature for immunotherapy and a proposed molecular subtyping scheme in gastric cancer

“…These proteins have the potential to serve as important prognostic biomarkers and therapeutic targets for esophageal cancer. [25] PER1 is one of the core components of the circadian clock gene [26], and participates in regulating many important physiological activities such as cell cycle and apoptosis. Current research suggests that PER1 is an important tumor suppressor.…”