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中国胰腺癌患者中PD-1/PD-L1表达与错配修复状态及促纤维增生性间质的预后价值和临床病理特征

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

作者信息

Wang Yu, Lin Jiacheng, Cui Jiujie, Han Ting, Jiao Feng, Meng Zhuo, Wang Liwei

机构信息

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.

出版信息

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.

摘要

胰腺癌(PC)是一种致死率很高的癌症。因此,有助于筛选PC患者的免疫分子标志物尤为重要。在本研究中,我们旨在系统分析错配修复蛋白1(MLH1)、错配修复蛋白2(MSH2)、程序性死亡配体1(PD-L1)和程序性死亡受体1(PD-1)的表达情况,探讨它们的临床意义和预后价值。我们发现,癌细胞膜上PD-L1的高表达与淋巴结转移相关(P = 0.033),且与低分化密切相关(P = 0.008);T细胞膜上PD-1的高表达与高分化相关(P = 0.018),且与T分期晚期密切相关(P = 0.004);高PD-1表达与显著更好的总生存期相关,并且是一个独立的预后因素(P = 0.031)。然后我们发现MSH2表达与PD-L1表达呈负相关(Spearman相关系数r = -0.295,P = 0.004)。在亚组分析中,我们观察到仅在低PD-L1表达亚组中,PD-1表达水平与总生存期相关(P = 0.021)。最后,当我们根据PD-1表达和基质密度将病例分为四个亚组时,我们发现PD-1高表达且基质致密的患者总生存期较好,而PD-1低表达且基质中等的患者预后最差。我们的结果可能为临床实践中PC患者的免疫治疗策略提供更有效的分子标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee3c/5354736/ea698ef95f18/oncotarget-08-9354-g001.jpg

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