Prognostic value and clinicopathological features of PD-1/PD-L1 expression with mismatch repair status and desmoplastic stroma in Chinese patients with pancreatic cancer

Oncotarget. 2017 Feb 7;8(6):9354-9365. doi: 10.18632/oncotarget.14069.

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.

Keywords: PD-1/PD-L1; mismatch repair enzymes; pancreatic cancer; prognosis.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / analysis*
  • Biomarkers, Tumor / analysis*
  • Cell Differentiation
  • China
  • DNA Mismatch Repair*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • MutL Protein Homolog 1 / analysis
  • MutS Homolog 2 Protein / analysis
  • Neoplasm Staging
  • Pancreatic Neoplasms / chemistry*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Programmed Cell Death 1 Receptor / analysis*
  • Proportional Hazards Models
  • Stromal Cells / pathology*
  • Time Factors
  • Tissue Array Analysis
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • MLH1 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein