Abstract

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.

Highlights

  • Pancreatic cancer (PC) is a highly lethal cancer, with a 5-year survival of approximately 5% [1,2]

  • MLH1 and MSH2 were distributed in the nucleus, while programmed death-1 (PD-1)/Program death ligand 1 (PD-L1) was located on cell membranes

  • MLH1 was highly expressed in 63.8% (60/94) of PC samples (Figure 1A, 1B), while MSH2 was highly expressed in 75.5% (71/94) of PC samples (Figure 1C, 1D)

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Summary

Introduction

Pancreatic cancer (PC) is a highly lethal cancer, with a 5-year survival of approximately 5% [1,2]. Surgery, radiotherapy and chemotherapy for pancreatic cancer have been improved, but the effect was limited. It is very important to find more effective molecular markers for the treatment and prognosis of PC patients in clinical practice. As a receptor of PD-L1, programmed death-1 (PD-1) is typically expressed on activated T cells. The antibodies of PD-1/ PD-L1 have shown improving outcome in patients with melanoma, renal cell carcinoma, non-small lung cancer, the results of treating pancreatic cancer with single-agent immune checkpoint inhibitors have been disappointing [10,11,12,13]. The immune molecular markers which help to select PC patients are especially important [14]

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