title: Prognostic value and clinicopathological features of PD-1/PD-L1 expression with mismatch repair status and desmoplastic stroma in Chinese patients with pancreatic cancer.
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.
authors.affiliation: Department of Medical Oncology and Pancreatic Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China.|Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China.|Shanghai Key Laboratory of Pancreatic Disease, Shanghai 201620, China.|State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Pancreatic Disease, Shanghai 201620, China.|State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China.|Shanghai Key Laboratory of Pancreatic Disease, Shanghai 201620, China.|State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Jiujie
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Medical Oncology and Pancreatic Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China.|Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China.|Shanghai Key Laboratory of Pancreatic Disease, Shanghai 201620, China.|State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China.|Shanghai Key Laboratory of Pancreatic Disease, Shanghai 201620, China.|State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiao
authors.affiliation: Department of Medical Oncology and Pancreatic Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China.|Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China.|Shanghai Key Laboratory of Pancreatic Disease, Shanghai 201620, China.|State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Medical Oncology and Pancreatic Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China.|Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China.|Shanghai Key Laboratory of Pancreatic Disease, Shanghai 201620, China.|State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D002681:China; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000032:analysis; D051718:MutS Homolog 2 Protein / Q000032:analysis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D016016:Proportional Hazards Models; D017154:Stromal Cells / Q000473:pathology*; D013997:Time Factors; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C501486:MLH1 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: PD-1/PD-L1; mismatch repair enzymes; pancreatic cancer; prognosis