Author(s)

Cailing Jiang¹, Chunyan Dang¹, Ruilong He¹, Limin Cheng², Yiying Bai¹, Xinyu Bai¹, Xin Wang¹, Qianhui Chen¹, Hongbin Yang³, Zhengxin Zhang⁴, Xiaotong Zhang³, Yan Chen⁴, Qian Xu⁴, Lei Liu^3*, Li Zhang^1*

¹Department of Oncology, The Affiliated Hospital of Chengde Medical University, Chengde, China.
²Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde, China.
³Department of Immunology, Chengde Medical University, Chengde, China.
⁴Department of Pathology, Chengde Medical University, Chengde, China.

Background: Pancreatic cancer is one of the most lethal types of cancer, and immunotherapy has become a promising remedy with advancements in tumor immunology. However, predicting the clinical response to immunotherapy in pancreatic cancer remains a dilemma for clinicians. Methods: GEPIA database was used to analyze the differential expression of MMR and PD-L1 genes in 33 common cancer types including pancreatic cancer. The expression levels of MMR and PD-L1 genes were downloaded from the GEPIA and GEO databases to analyze the correlation between MMR genes and PD-L1, and the clinicopathological and survival information were downloaded from the TCGA databases to analyze the relationship between the expression of MMR, PD-L1 and clinicopathological characteristics, prognosis. Meanwhile, the tumor tissue samples of 41 patients with pancreatic cancer were collected, and the protein expression levels of MMR and PD-L1 were detected by immunohistochemical assay. Furthermore, we analyzed the correlation between MMR and PD-L1, and the correlation between the expression of MMR, PD-L1 and clinicopathological characteristics, prognosis of pancreatic cancer patients. Results: Bioinformatics analysis showed that MLH1, MLH3, MSH2, MSH3, and PMS2 were highly expressed in most cancer types including pancreatic cancer (P < 0.05). TCGA data revealed that MLH1 expression was related to gender (P = 0.012), clinical stage (I vs II: P = 0.016), MSH2 expression was related to clinical stage (P < 0.05), T stage (T3 vs T4: P = 0.039), and MSH3 expression was related to T stage (P < 0.05). Besides, both MSH2 expression (P < 0.001) and MSH6 (P = 0.044) were significantly associated with prognosis. GEPIA data also showed that MSH2 expression was related to prognosis (P = 0.008). The correlation analysis revealed that the expressions MSH2, MLH1, PMS2 had strong correlations with PD-L1 both in GEPIA and GEO databases. Real-world data indicated that of the 41 pancreatic cancer patients, 5 cases had MLH1 deletion, 5 cases had MSH2 deletion, 4 cases had PMS2 deletion, and 12 cases had PD-L1 positive expression. Notably, PMS2 deletion was associated with PD-L1 positive expression (P = 0.035). In addition, MLH1 was related to clinical stage (P = 0.033), age (P = 0.048), and MSH2 was related to clinical stage (P = 0.033). However, MLH1 (P = 0.697), MSH2 (P = 0.956), PMS2 (P = 0.341), and PD-L1 (P = 0.734) appeared to have no impact on overall survival among patients with pancreatic cancer. Conclusion: Both bioinformatics and real-world data showed that there were correlation between PMS2 deletion and PD-L1 expression, and correlation between MLH1, MSH2 and clinical stage.

Pancreatic Cancer, PD-L1, PMS2, Mismatch Repair Protein, Correlation

Jiang, C. , Dang, C. , He, R. , Cheng, L. , Bai, Y. , Bai, X. , Wang, X. , Chen, Q. , Yang, H. , Zhang, Z. , Zhang, X. , Chen, Y. , Xu, Q. , Liu, L. and Zhang, L. (2023) Positive Correlation between PMS2 Deficiency and PD-L1 Expression in Pancreatic Cancer. Advances in Bioscience and Biotechnology, 14, 74-90. doi: 10.4236/abb.2023.142005.