Anoikis resistance regulates immune infiltration and drug sensitivity in clear-cell renal cell carcinoma: insights from multi omics, single cell analysis and in vitro experiment

Wen, Xiangyang and Hou, Jian and Qi, Tiantian and Cheng, Xiaobao and Liao, Guoqiang and Fang, Shaohong and Xiao, Song and Qiu, Longlong and Wei, Wanqing (2024) Anoikis resistance regulates immune infiltration and drug sensitivity in clear-cell renal cell carcinoma: insights from multi omics, single cell analysis and in vitro experiment. Frontiers in Immunology, 15. ISSN 1664-3224

[thumbnail of fimmu-15-1427475.pdf] Text
fimmu-15-1427475.pdf - Published Version

Download (16MB)

Abstract

Background: Anoikis is a form of programmed cell death essential for preventing cancer metastasis. In some solid cancer, anoikis resistance can facilitate tumor progression. However, this phenomenon is underexplored in clear-cell renal cell carcinoma (ccRCC).

Methods: Using SVM machine learning, we identified core anoikis-related genes (ARGs) from ccRCC patient transcriptomic data. A LASSO Cox regression model stratified patients into risk groups, informing a prognostic model. GSVA and ssGSEA assessed immune infiltration, and single-cell analysis examined ARG expression across immune cells. Quantitative PCR and immunohistochemistry validated ARG expression differences between immune therapy responders and non-responders in ccRCC.

Results: ARGs such as CCND1, CDKN3, PLK1, and BID were key in predicting ccRCC outcomes, linking higher risk with increased Treg infiltration and reduced M1 macrophage presence, indicating an immunosuppressive environment facilitated by anoikis resistance. Single-cell insights showed ARG enrichment in Tregs and dendritic cells, affecting immune checkpoints. Immunohistochemical analysis reveals that ARGs protein expression is markedly elevated in ccRCC tissues responsive to immunotherapy.

Conclusion: This study establishes a novel anoikis resistance gene signature that predicts survival and immunotherapy response in ccRCC, suggesting that manipulating the immune environment through these ARGs could improve therapeutic strategies and prognostication in ccRCC.

Item Type: Article
Subjects: Universal Eprints > Multidisciplinary
Depositing User: Managing Editor
Date Deposited: 17 Jun 2024 08:06
Last Modified: 17 Jun 2024 08:06
URI: http://journal.article2publish.com/id/eprint/3861

Actions (login required)

View Item
View Item