Pan-cancer analysis of prognostic and immunological role of IL4I1 in human tumors: a bulk omics research and single cell sequencing validation

Bin Chen; Yi Liu; Yuping He; Chenfu Shen

doi:10.1007/s12672-024-01000-5

Pan-cancer analysis of prognostic and immunological role of IL4I1 in human tumors: a bulk omics research and single cell sequencing validation

Discov Oncol. 2024 May 1;15(1):139. doi: 10.1007/s12672-024-01000-5.

Authors

Bin Chen^{1

2}, Yi Liu³, Yuping He^{4

5}, Chenfu Shen^{6

7}

Affiliations

¹ Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁴ Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan, China. ypinghe2022@126.com.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. ypinghe2022@126.com.
⁶ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. scf680524@csu.edu.cn.
⁷ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. scf680524@csu.edu.cn.

Abstract

Background: Interleukin-4 inducible gene 1 (IL4I1) regulates tumor progression in numerous tumor types. However, its correlation with immune infiltration and prognosis of patients in a pan-cancer setting remains unclear.

Methods: Data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN, Clinical Proteomic Tumor Analysis Consortium (CPTAC), Gene Expression Omnibus (GEO), cBioPortal, Cancer Single-cell State Atlas (CancerSEA), and Tumor IMmune Estimation Resource(TIMER) databases were used to evaluate IL4I1 expression, clinical features and prognostic effects, gene set enrichment, and correlation with immune cell infiltration, as well as the relationship between IL4I1 methylation and expression and survival prognosis. Correlations with 192 anticancer drugs were also analyzed.

Results: IL4I1 was significantly overexpressed in the majority of tumors, and the imbalance of IL4I1 was significantly correlated with overall survival and pathological stage. Moreover, total IL4I1 protein was increased in cancer. Therefore, IL4I1 may be used as a prognostic biomarker or protective factor in numerous types of cancer. The methylation level of IL4I1 may also be used as a prognostic marker. The functional enrichment of IL4I1 was closely related to the immunomodulatory pathway. In addition, the level of tumor-associated macrophage infiltration was positively correlated with the expression of IL4I1 in pan-cancerous tissues. scRNA-seq analysis suggested that IL4I1 differ significantly among different cells in the tumor microenvironment and was most enriched in macrophages. Various immune checkpoint genes were positively correlated with IL4I1 expression in most tumors. In addition, patients with high IL4I1 expression may be resistant to BMS-754807 and docetaxel, but sensitive to temozolomide.

Conclusion: IL4I1 may play a role as promoter of cancer and prognostic indicator in patients. High expression of IL4I1 is associated with the state of tumor immunosuppression and may contribute to tumor-associated macrophage invasion. Therefore, IL4I1 may be a new therapeutic target for the treatment and prognosis of patients with cancer.

Keywords: Interleukin-4 inducible gene 1; Pan-cancer; Tumor immune microenvironment; Tumor immunosuppressive status; Tumor-associated macrophages.

Grants and funding

2021JJ70074/Hunan Provincial Natural Science Committee Project