TITLE:
Positive Correlation between PMS2 Deficiency and PD-L1 Expression in Pancreatic Cancer
AUTHORS:
Cailing Jiang, Chunyan Dang, Ruilong He, Limin Cheng, Yiying Bai, Xinyu Bai, Xin Wang, Qianhui Chen, Hongbin Yang, Zhengxin Zhang, Xiaotong Zhang, Yan Chen, Qian Xu, Lei Liu, Li Zhang
KEYWORDS:
Pancreatic Cancer, PD-L1, PMS2, Mismatch Repair Protein, Correlation
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.14 No.2,
February
24,
2023
ABSTRACT: 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
andclinicopathological 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 P = 0.012), clinical stage (I vs II: P = 0.016), MSH2
expression was related to clinical stage (P P = 0.039), and MSH3 expression was related to T stage (P P 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.