Expression of ZNF281 in colorectal cancer correlates with response to radiotherapy and survival

Abstract

Background

The treatment of Colorectal cancer (CRC) is extremely complex and survival rates vary depending on the stage of the disease at the time of diagnosis. Neoadjuvant chemoradiotherapy (NACRT), is the conventional treatment for locally advanced rectal cancer (LARC); however, the resistance to chemoradiotherapy in LARC is difficult to predict.

Materials and methods

In this study, clinical data of 126 LARC patients were collected and analyzed, and relevant validation was performed using GEO database and in vitro and in vivo experiments, including Western blotting and Real-time quantitative PCR, immunohistochemistry, immunofluorescence, clonogenic cell survival assays, and nude-mouse xenograft models.

Results

In patients with LARC who were treated with neoadjuvant radiotherapy (NART), higher ZNF281 expression in malignant tissue was associated with a poorer prognosis and lesser degree of tumor regression. Cell and mouse experiments have shown that ZNF281 reduces the damage caused by X-rays to CRC cells and tumors grown in mice.

Conclusion

We found that the expression of ZNF281 predicted the radiation response of CRC cells and suggested the prognosis of patients with LARC who received neoadjuvant radiation therapy.

Keywords:

• ZNF281
• Colorectal cancer
• radioresistance
• DNA damage repair
• prognosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

C.Q. contributed to the conception and design of this paper. A.L., Y.X. organized this paper. A.L., Y.X., W.L. undertook the relevant experimental work. A.L., Y.X., W.L., E.Z. and Q.L. contributed to all tables and figures and the main manuscript. H.J., Y.Z., H.Z. and X.M. collected pathological sections and stained them for analysis. H.T. and D.R. revised and supplemented the manuscript. All of the authors read and approved the final manuscript.

Availability of data and materials

The data used to support the findings of this study are included within the article.

Consent for publication

We assure that the material is original, and it has not been published elsewhere yet.

Additional information

Funding

This study was supported by Natural Science Foundation of Henan Province (232300420049), Science and Technology Foundation of Henan Province (SBGJ202002097, 192102310099), Henan Provincial Education Fund (19A320020), Postgraduate Cultivating Innovation and Quality Improvement Action Plan of Henan University (SYLYC2022141, SYLYC2023124), Henan Province United Common Project Fund (LHGJ20220663), Henan Provincial Science and Technology Research Project (222102310134), Ruida Pharmaceutical Clinical Medicine Postgraduate Education Innovation Training Base Project of Henan University (SYLJD2022009), and Program for Innovative Research Team (in Science and Technology) in University of Henan Province (24IRTSTHN041).