High expression ITGA2 affects the expression of MET,PD-L1, CD4 and CD8 with the immune microenvironment in pancreatic cancer patients
Authors: Jin Liquan , Duan Yaoqiang , Li Zhengqi , Hu Jifu , Shi Hongbo , Su Ziting , li Zhe , Du Bilian , Chen Yiming , Tan Yunbo 
Published: May 2023

Abstract
Perpose:
Pancreatic cancer has a poor prognosis and is considered one of the most lethal tumors. ITGA2, a gene highly expressed in various tumor tissues, is a promising candidate for cancer therapy. The objective of this study is to assess the presence of ITGA2, MET and PD-L1 in pancreatic cancer, while also identifying ITGA2, CD4 and CD8 as potential survival indicators for patients suffering from this disease.
Experimental Design:
We examined the expression of ITGA2, MET, E-cad, PD-L1, CD4, and CD8 proteins in 62 pancreatic cancer tissue samples using multi-tissue immunofluorescence and immunohistochemistry techniques.This study examined how the protein expression of ITGA2, E-cad, and PD-L1 relate to clinicopathological features in patients diagnosed with pancreatic cancer. Additionally, the study examined the correlation between protein expression of ITGA2, CD4, and CD8 in pancreatic cancer and their relationship with clinicopathological features and prognosis.
Results
In our study, we observed the expression of ITGA2, E-cad, and PD-L1 in both tumor and stroma tissues of pancreatic cancer. Interestingly, the expression of E-cad and PD-L1 was higher in the stroma (average = 25.827% and average = 34.346%, respectively) compared to the tumor (average = 19.973% and average = 20.042%, respectively). Additionally, we found a positive correlation between ITGA2 and E-cad, as well as PD-L1 in the tumor region (r = 0.55, P < 0.001 and r = 0.51, P < 0.001, respectively), and PD-L1 in the stroma region (r = 0.51, P < 0.001).In this study, the correlation between ITGA2, E-cad, and PD-L1 with tumor marker CA-199 and lymph node metastasis was observed (P < 0.05). Additionally, the expression levels of ITGA2, CD4, and CD8 were found to be significantly higher in pancreatic cancer tissues compared to adjacent tissues (P < 0.05) as determined by immunohistochemical analysis.The protein expressions were found to be correlated with the degree of differentiation, TNM stage, lymph node metastasis, and local invasion in pancreatic cancer patients (all P < 0.05), while no significant correlation was observed with age, gender, tumor location, and tumor size (all P > 0.05).the study found that the protein expression of ITGA2 was negatively correlated with CD4 and CD8 (r = -0.344, P < 0.005 and r = -0.398, P < 0.005). The follow-up was successful in 95.0% of the 62 patients with pancreatic cancer, with a follow-up time ranging from 3 to 64 months. Furthermore, the study found that the expression of ITGA2, CD4, and CD8 was correlated with the survival time of patients after surgery (all P < 0.05).The study analyzed the clinicopathological data of 62 patients diagnosed with pancreatic cancer through univariate COX regression analysis. The findings indicated that the prognosis of patients was associated with various factors such as histological grade, TNM stage, local invasion, lymph node metastasis, and the expression intensity of ITGA2, CD4, and CD8 (all P < 0.05). However, multivariate regression analysis highlighted that only local invasion was an independent prognostic factor for overall survival (P < 0.05).
Conclusions
ITGA2 has been identified as a potential target for the treatment and prevention of pancreatic cancer. Studies have shown that increased expression of ITGA2 is associated with poor prognosis in pancreatic cancer patients, and may impact the immune microenvironment by affecting the expression of PD-L1, CD4, and CD8. This suggests that ITGA2 could serve as a valuable entry point for developing new therapies for pancreatic cancer.