Exploring the Expression and Prognosis of Mismatch Repair Proteins and PD-L1 in Colorectal Cancer in a Chinese Cohort

Lu Han; Yaping Zhang; Li Li; Qun Zhang; Zhihao Liu; Haiqing Niu; Jing Hu; Zhou Ding; Xiao Shi; Xiaoping Qian

doi:10.2147/CMAR.S417470

Exploring the Expression and Prognosis of Mismatch Repair Proteins and PD-L1 in Colorectal Cancer in a Chinese Cohort

Cancer Manag Res. 2023 Aug 7:15:791-801. doi: 10.2147/CMAR.S417470. eCollection 2023.

Authors

Lu Han^#^{1

2}, Yaping Zhang^#^{2

3

4}, Li Li^#², Qun Zhang², Zhihao Liu^{2

3}, Haiqing Niu^{1

2}, Jing Hu², Zhou Ding², Xiao Shi², Xiaoping Qian^{1

2}

Affiliations

¹ Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
² The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China.
³ Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, People's Republic of China.
⁴ Department of Pathology, The First People's Hospital of Yangzhou, Yangzhou, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Exploring the expression and prognosis of mismatch repair proteins and PD-L1 in colorectal cancer.

Patients and methods: A total of 272 patients with surgically resected CRC were enrolled in the study from January 2018 to May 2022 at Nanjing Drum Tower Hospital (The Affiliated Hospital of Nanjing University Medical School). Surgically resected samples were collected from patients along with general, clinicopathological, and imaging data for each patient. Immunohistochemistry (IHC) was used to detect expression of MSH2, MSH6, MLH1, and PMS2 proteins in tumor tissue. X-squared (X²) testing was performed to investigate the correlation between expression of MMR proteins and PD-L1 in CRC tumor tissues and clinicopathological characteristics. Correlation analysis was also used to compare the deletion of four MMR proteins in CRC tumor tissues. A survival curve and Log rank test were used to investigate the relationship between the expression of MMR proteins and PD-L1 with regard to CRC patient prognosis and survival.

Results: MMR protein expression deletion was correlated with tumor location, the degree of tissue differentiation, and TNM stage (P<0.05). PD-L1 expression was correlated with TNM stage (P<0.05). Correlation analysis of deletion of MMR protein isoform expression found that PMS2 deletion was significantly correlated with MLH1 deletion (P<0.05). Similarly, MSH2 deletion was significantly correlated with MSH6 deletion (P<0.05). PMS2 deletion was also found to be correlated with PD-L1 expression (P<0.05). Progression-free survival was found to be significantly longer in mismatch repair-proficient (pMMR) patients compared with mismatch repair-deficient (dMMR) patients.

Conclusion: Deletion of MMR proteins and expression of PD-L1 are closely related to clinicopathological characteristics and overall prognosis of CRC patients. This suggests the relevance of MMR and PD-L1 as potential biomarkers for treatment of CRC patients.

Keywords: IHC; MMR; pathological features; survival analysis.

Grants and funding

This study was supported by grants from Nanjing health science and technology development key program (no ZKX21028), Provincial Natural Science Foundation of Jiangsu (no BK20211007), Jiangsu scientific and technological development of traditional Chinese medicine Key projects (no ZD202227).