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

  • Translational Research
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Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Funding

This work was supported by grants from the National Natural Science Foundation of China [81802995], Zhejiang Province Public Welfare Funds [LGF19H280004].

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Author notes

  1. Xiaoling Xu and Ding Wang have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Thoracic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou City, China

    Xiaoling Xu MD, Jiamin Sheng MM & Yun Fan MD

  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

    Xiaoling Xu MD, Jiamin Sheng MM, Guoping Cheng MM & Yun Fan MD

  3. The Second Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, China

    Xiaoling Xu MD, Ding Wang MM, Na Li MM, Mingying Xie MM, Zichao Zhou MM, Guoping Cheng MM & Yun Fan MD

  4. Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China

    Guoping Cheng MM

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Contributions

Conceptualization: Y.F. and G.C. Methodology: X.X. and D.W. Investigation: X.X. and N.L. Bioinformatics analysis: X.X. and J.S. Writing, original draft: X.X. and M.X. Writing, review and editing: Z.Z. Funding acquisition: X.X. Supervision: Y.F. and G.C. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Yun Fan MD.

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Xu, X., Wang, D., Li, N. et al. The Novel Tumor Microenvironment-Related Prognostic Gene AIF1 May Influence Immune Infiltrates and is Correlated with TIGIT in Esophageal Cancer. Ann Surg Oncol 29, 2930–2940 (2022). https://doi.org/10.1245/s10434-021-10928-9

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