Prognostic value and clinicopathological features of PD-1/PD-L1 expression with mismatch repair status and desmoplastic stroma in Chinese patients with pancreatic cancer
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Yu Wang1,2,3,4,*, Jiacheng Lin3,4,*, Jiujie Cui2,3,4,*, Ting Han1,2,3,4, Feng Jiao2,3,4, Zhuo Meng1,2,3,4, Liwei Wang1,2,3,4
1Department of Medical Oncology and Pancreatic Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China
2Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China
3Shanghai Key Laboratory of Pancreatic Disease, Shanghai 201620, China
4State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
*These authors are contributed equally to this work
Liwei Wang, email: [email protected]
Keywords: PD-1/PD-L1, mismatch repair enzymes, pancreatic cancer, prognosis
Received: September 27, 2016 Accepted: December 16, 2016 Published: December 21, 2016
Pancreatic cancer (PC) is a highly lethal cancer. Thus, the immune molecular markers which help to select PC patients are especially important. In this study, we aimed at systematically analyzing the expression of MLH1, MSH2, PD-L1 and PD-1, investigate their clinical significance and prognostic value. We found that high expression of PD-L1 on cancer cell membranes correlated with lymph node metastasis (P = 0.033) and strongly correlated with poor-differentiation (P = 0.008); high expression of PD-1 on cell membranes of T-cells correlated with well-differentiation (P = 0.018) and strongly correlated with advanced T stage (P = 0.004); high PD-1 expression was associated with a significantly superior OS and was an independent prognostic factor (P = 0.031). Then we found an inverse correlation between MSH2 expression and PD-L1 expression (Spearman correlation coefficient r = −0.295, P = 0.004). In subgroup analyses, we observed that PD-1 expression level was associated with OS only at low PD-L1 expression subgroup (P = 0.021). Finally, when we stratified the cases into four subgroups based on PD-1 expression and stroma density, we found that patients with high PD-1 expression and dense stroma had a better OS, while patients with low PD-1 expression and moderate stroma showed a worst outcome. Our result may provide more effective molecular markers for immunotherapeutic strategies of PC patients in clinical practice.
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