The Novel Tumor Microenvironment-Related Prognostic Gene AIF1 May Influence Immune Infiltrates and is Correlated with TIGIT in Esophageal Cancer

• Published in: Annals of surgical oncology 2022-05, Vol.29 (5), p.2930-2940
• Main Authors: Xu, Xiaoling, Wang, Ding, Li, Na, Sheng, Jiamin, Xie, Mingying, Zhou, Zichao, Cheng, Guoping, Fan, Yun
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cancer; DNA microarrays; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - genetics; Esophageal Squamous Cell Carcinoma - genetics; Esophagus; Gene Expression Regulation, Neoplastic; Genes; Genomes; Humans; Immunofluorescence; Immunoglobulins; Immunohistochemistry; Immunoreceptor tyrosine-based inhibition motif; Immunotherapy; Inflammation; Lymphocytes T; Medical prognosis; Medicine; Medicine & Public Health; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Oncology; Patients; Prognosis; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Squamous cell carcinoma; Surgery; Surgical Oncology; Transcriptomics; Translational Research; Tumor Microenvironment; Tumors
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-021-10928-9

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.