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淋巴细胞激活基因-3(LAG-3)表达在食管鳞状细胞癌中的预后价值

Prognostic Value of Lymphocyte Activation Gene-3 (LAG-3) Expression in Esophageal Squamous Cell Carcinoma.

作者信息

Zhang Yu, Liu Yong-Dong, Luo Yi-Ling, Liu Bin-Liu, Huang Qi-Tao, Wang Fang, Zhong Qian

机构信息

Department of Pathology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou 510060, China.

Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, No. 58th Zhongshan 2nd Road, Guangzhou 510080, China.

出版信息

J Cancer. 2018 Oct 20;9(22):4287-4293. doi: 10.7150/jca.26949. eCollection 2018.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor with a high incidence in East Asia and the Middle East. The outcomes for ESCC patients are usually not optimal due to the recurrence and metastasis. This study is aim to examine the expression and the prognostic value of LAG-3 in ESCC. We applied immunohistochemistry analysis to examine the expression of LAG-3, CD4 and CD8 in 287 ESCC cohorts. Our study demonstrated that the decreased LAG-3 expression was significantly associated with CD4 tumor-infiltrated lymphocytes (TILs) (=0.000), CD8 TILs (=0.000), and the advanced clinical stages (=0.041) by Chi-square analysis. Kaplan-Meier survival analysis revealed that higher LAG-3 expression were positively correlated with a better overall survival (OS) (=0.010) and better progression free survival (PFS) (=0.006), especially in the patients at stages T1-2 status (=0.001, OS; =0.001, PFS), N0 status (=0.036, OS; =0.050, PFS), and early stages (I-II) (=0.006, OS; =0.008, PFS). Both high of CD4 TIL /CD8 TIL ratio and LAG-3 expression were correlated with longer OS and PFS. Cox proportional hazards regression analysis showed that LAG-3 is an independent biomarker of survival (HR, 0.724; 95% CI 0.526-0.995; = 0.047) (=0.036). Taken together, we found that high expression of LAG-3 was correlated with an improved survival and LAG-3 is an independent predictor of survival, suggesting that LAG-3 may serve as a useful immune marker for the prognosis of ESCC.

摘要

食管鳞状细胞癌(ESCC)是一种恶性上皮性肿瘤,在东亚和中东地区发病率较高。由于复发和转移,ESCC患者的治疗结果通常并不理想。本研究旨在检测ESCC中淋巴细胞活化基因3(LAG-3)的表达及其预后价值。我们应用免疫组织化学分析检测了287例ESCC患者队列中LAG-3、CD4和CD8的表达。我们的研究表明,通过卡方分析,LAG-3表达降低与CD4肿瘤浸润淋巴细胞(TILs)(P = 0.000)、CD8 TILs(P = 0.000)及临床晚期(P = 0.041)显著相关。Kaplan-Meier生存分析显示,较高的LAG-3表达与较好的总生存期(OS)(P = 0.010)和无进展生存期(PFS)(P = 0.006)呈正相关,尤其是在T1-2期(P = 0.001,OS;P = 0.001,PFS)、N0期(P = 0.036,OS;P = 0.050,PFS)和早期(I-II期)(P = 0.006,OS;P = 0.008,PFS)患者中。高CD4 TIL/CD8 TIL比值和LAG-3表达均与更长的OS和PFS相关。Cox比例风险回归分析显示,LAG-3是生存的独立生物标志物(HR,0.724;95%CI 0.526 - 0.995;P = 0.047)(P = 0.036)。综上所述,我们发现LAG-3高表达与生存改善相关,且LAG-3是生存的独立预测因子,提示LAG-3可能作为ESCC预后的有用免疫标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6793/6277627/61e87ff72fa6/jcav09p4287g001.jpg

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