Xiaoling Xu1,2,3, Ding Wang3, Na Li3, Jiamin Sheng1,2, Mingying Xie3, Zichao Zhou3, Guoping Cheng2,3,4, Yun Fan5,6,7. 1. Department of Thoracic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou City, China. 2. Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou City, China. 3. The Second Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, China. 4. Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China. 5. Department of Thoracic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou City, China. fanyun1218@163.com. 6. Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou City, China. fanyun1218@163.com. 7. The Second Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, China. fanyun1218@163.com.
Abstract
BACKGROUND: Esophageal carcinoma (EC) is the sixth most common cause of cancer-related mortality worldwide. Studying the associations of the tumor microenvironment (TME) with pathology and prognosis would illustrate the underlying mechanism of prognostic prediction and provide novel targets for immunotherapy in the treatment of EC. METHODS: Transcriptomic profiles of 159 EC patients were obtained from The Cancer Genome Atlas (TCGA) database. Stromal and immune scores were calculated using the ESTIMATE algorithm. Differentially expressed genes (DEGs) were identified by the optimal score cutoff. Functional enrichments were analyzed by DAVID, while prognostic genes were explored using the Kaplan-Meier method. Validation analysis was performed using immunohistochemistry in tissue microarrays containing samples from 145 EC patients. Multiplex immunofluorescence staining was performed to detect a panel of 6 immune markers, including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), in 90 EC patients. RESULTS: Immune scores significantly increased with increasing age, while stromal scores were dramatically elevated with increasing tumor stage. Fifteen TME-related DEGs including allograft inflammatory factor 1 (AIF1) were identified as prognostic factors of EC. Furthermore, the validation cohort indicated that AIF1 was negatively associated with the prognosis of esophageal squamous cell carcinoma patients. Subsequent analyses suggested that AIF1 may affect immune infiltrates, including T cells and natural-killer cells. Moreover, a correlation between AIF1 and TIGIT was identified. CONCLUSIONS: These results indicate that the TME-related gene AIF1 is a promising predictor of prognosis and is related to immune infiltrates and TIGIT expression in EC. However, further mechanistic studies are needed.
BACKGROUND: Esophageal carcinoma (EC) is the sixth most common cause of cancer-related mortality worldwide. Studying the associations of the tumor microenvironment (TME) with pathology and prognosis would illustrate the underlying mechanism of prognostic prediction and provide novel targets for immunotherapy in the treatment of EC. METHODS: Transcriptomic profiles of 159 EC patients were obtained from The Cancer Genome Atlas (TCGA) database. Stromal and immune scores were calculated using the ESTIMATE algorithm. Differentially expressed genes (DEGs) were identified by the optimal score cutoff. Functional enrichments were analyzed by DAVID, while prognostic genes were explored using the Kaplan-Meier method. Validation analysis was performed using immunohistochemistry in tissue microarrays containing samples from 145 EC patients. Multiplex immunofluorescence staining was performed to detect a panel of 6 immune markers, including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), in 90 EC patients. RESULTS: Immune scores significantly increased with increasing age, while stromal scores were dramatically elevated with increasing tumor stage. Fifteen TME-related DEGs including allograft inflammatory factor 1 (AIF1) were identified as prognostic factors of EC. Furthermore, the validation cohort indicated that AIF1 was negatively associated with the prognosis of esophageal squamous cell carcinoma patients. Subsequent analyses suggested that AIF1 may affect immune infiltrates, including T cells and natural-killer cells. Moreover, a correlation between AIF1 and TIGIT was identified. CONCLUSIONS: These results indicate that the TME-related gene AIF1 is a promising predictor of prognosis and is related to immune infiltrates and TIGIT expression in EC. However, further mechanistic studies are needed.
Authors: Tanguy Y Seiwert; Barbara Burtness; Ranee Mehra; Jared Weiss; Raanan Berger; Joseph Paul Eder; Karl Heath; Terrill McClanahan; Jared Lunceford; Christine Gause; Jonathan D Cheng; Laura Q Chow Journal: Lancet Oncol Date: 2016-05-27 Impact factor: 41.316