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

Research Paper

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

Yu Zhang1*, Yong-dong Liu2*, Yi-ling Luo3, Bin-liu Liu3, Qi-tao Huang1, Fang Wang4✉, Qian Zhong3✉

1. Department of Pathology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou 510060, China
2. Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, No. 58th Zhongshan 2nd Road, Guangzhou 510080, China
3. State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou 510060, China
4. Department of Molecular Diagnosis, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou 510060, China
*Equal contributors

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) (p=0.000), CD8 TILs (p=0.000), and the advanced clinical stages (p=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) (p=0.010) and better progression free survival (PFS) (p=0.006), especially in the patients at stages T1-2 status (p=0.001, OS; p=0.001, PFS), N0 status (p=0.036, OS; p=0.050, PFS), and early stages (I-II) (p=0.006, OS; p=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; p = 0.047) (p=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.

Keywords: LAG-3, ESCC, TIL, prognosis

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How to cite this article:
Zhang Y, Liu Yd, Luo Yl, Liu Bl, Huang Qt, Wang F, Zhong Q. Prognostic Value of Lymphocyte Activation Gene-3 (LAG-3) Expression in Esophageal Squamous Cell Carcinoma. J Cancer 2018; 9(22):4287-4293. doi:10.7150/jca.26949. Available from http://www.jcancer.org/v09p4287.htm