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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1642193

This article is part of the Research TopicCommunity Series in Tumor Microenvironment and Metabolic Reprogramming in Cancer: Volume IIView all 7 articles

Functional Characterization and Clinical Significance of IGSF8 in Pan-Cancer: An Integrated Bioinformatic and Experimental Study

Provisionally accepted
  • 1West China Hospital of Sichuan University, Chengdu, China
  • 2Taizhou Hospital of Zhejiang Province, Linhai, China
  • 3University College London, London, United Kingdom
  • 4Zhejiang Chinese Medical University, Hangzhou, China
  • 5Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, China

The final, formatted version of the article will be published soon.

Immunoglobulin superfamily member 8 (IGSF8) is a membrane protein implicated in crucial biological processes like cell interactions and immune responses. Emerging evidence suggests that IGSF8 plays a significant role in various cancers by influencing tumor progression through regulation of cell proliferation, migration, and apoptosis. Analyzing its expression, mutation status, and clinical correlations across different cancer types through pan-cancer bioinformatics could provide valuable insights into its potential as a biomarker and target for cancer therapies.In this study, we utilized several public databases to investigate the biological role of IGSF8, focusing on its associations with prognosis, tumor heterogeneity, stemness, immune checkpoint genes, and immune cell infiltration across different types of cancer. Additionally, the GDSC and CTRP databases were employed to assess the sensitivity of IGSF8 to small molecule drugs. CCK8 assay and colony formation assay were used to detect its biological effect on cancer cells.IGSF8 was significantly upregulated in 23 types of cancers and associated with poor prognosis in several cancers, including cell carcinoma and endocervical adenocarcinoma (CESC) and Acute Myeloid Leukemia(LAML). Its high expression was linked to multiple immune regulatory genes and immune checkpoint genes in the tumor microenvironment, with a notable positive correlation with CD276 in most cancers. IGSF8 was also closely associated with multiple indicators of tumor heterogeneity, stemness, as well as significant RNA methylation modifications across various cancers. Drug sensitivity analysis identified BX-795 and tozasertib as potential treatments for tumors with high IGSF8 expression. Knockdown of IGSF8 significantly inhibited the proliferation ability of prostate cancer cells.Our findings indicated that IGSF8 might be used as a potential prognostic marker and therapeutic target for various cancers.

Keywords: Immunoglobulin superfamily member 8, Pan-cancer analysis, Tumor immune microenvironment, drug sensitivity, tumor biomarker

Received: 06 Jun 2025; Accepted: 04 Aug 2025.

Copyright: © 2025 Wang, Lu, Wu, Li, Wang, Ye and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dechao Feng, University College London, London, United Kingdom

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