Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients.

Vincent Ho,Tara L Roberts,Askar Abubakar,Cheok Soon Lee,Paul De Souza,Mark Lee,Wei Chua,Amandeep Singh,Weng Ng,Liping Chung,Stephanie H Lim,Vivienne Lea

doi:10.3390/ijms21051768

Abstract

The DNA damage response enables cells to survive and maintain genome integrity. RAD52 is a DNA-binding protein involved in the homologous recombination in DNA repair, and is important for the maintenance of tumour genome integrity. We investigated possible correlations between RAD52 expression and cancer survival and response to preoperative radiotherapy. RAD52 expression was examined in tumour samples from 179 patients who underwent surgery for rectal cancer, including a sub-cohort of 40 patients who were treated with neoadjuvant therapy. A high score for RAD52 expression in the tumour centre was significantly associated with worse disease-free survival (DFS; p = 0.045). In contrast, reduced RAD52 expression in tumour centre samples from patients treated with neoadjuvant therapy (n = 40) significantly correlated with poor DFS (p = 0.025) and overall survival (OS; p = 0.048). Our results suggested that RAD52 may have clinical value as a prognostic marker of tumour response to neoadjuvant radiation and both disease-free status and overall survival in patients with rectal cancer.

Highlights

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, and is a major cause of cancer mortality worldwide
We found that high levels of post-operative RAD52 expression in the tumour centre (TC) correlated with worse disease-free survival (DFS) and overall survival (OS) compared with low RAD52 expression
Our findings show that RAD52 expression is a potential prognostic factor for rectal cancer, with elevated levels of RAD52 predicting poor survival outcome

Summary

Introduction

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, and is a major cause of cancer mortality worldwide. Surgical resection remains a primary treatment modality for all types of CRC, the surgical resectability of cancers of the colon and rectum determines their distinct clinical management. Limited access within the pelvic cavity and proximity to the mesorectal fascia and pelvic organs makes resection with clear margins of rectal cancers challenging, leading to a high risk of local recurrence [2]. Preoperative or neoadjuvant radiotherapy, in combination with 5-fluorouracil (5-FU), has produced significant improvements in clinical outcomes, such as decreased rate of local recurrence and reduced surgery-related morbidities, which has helped establish this approach as the standard of care for treatment of rectal cancer, especially for larger or slightly more advanced tumours, prior to resection [3]. Pathologic complete response, determined by the lack of a viable tumour after treatment, is seen in

Objectives

Methods

Results

Discussion

Conclusion