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Journal of Cancer Research and Clinical Oncology

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Open Access 01-03-2024 | Breast Cancer | Research

PIK3CA mutation-driven immune signature as a prognostic marker for evaluating the tumor immune microenvironment and therapeutic response in breast cancer

Authors: Xueting Ren, Hanxiao Cui, Luyao Dai, Lidan Chang, Dandan Liu, Wenyu Yan, Xuyan Zhao, Huafeng Kang, Xiaobin Ma

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2024

Abstract

Purpose

Gene mutations drive tumor immune microenvironment (TIME) heterogeneity, in turn affecting prognosis and immunotherapy efficacy. PIK3CA is the most frequently mutated gene in breast cancer (BC), yet its relevance to BC prognosis remains controversial. Herein, we sought to determine the impact of PIK3CA mutation-driven immune genes (PDIGs) on BC prognosis in relation to TIME heterogeneity.

Methods

PIK3CA mutation characteristics were compared and verified between the TCGA-BRCA dataset and a patient cohort from our hospital. PIK3CA mutation-driven differentially expressed genes were identified for consensus clustering and weighted gene co-expression network analysis to select the modules most relevant to the immune subtype. Thereafter, the two were intersected to obtain PDIGs. Univariate Cox, LASSO, and multivariate Cox regression analyses were sequentially performed on PDIGs to obtain a PIK3CA mutation-driven immune signature (PDIS), which was then validated using the Gene Expression Omnibus (GEO) database. Differences in functional enrichment, mutation landscape, immune infiltration, checkpoint gene expression, and drug response were compared between different risk groups.

Results

PIK3CA mutation frequencies in the TCGA and validation cohorts were 34.49% and 40.83%, respectively. PIK3CA mutants were significantly associated with ER, PR, and molecular BC subtypes in our hospital cohort. The PDIS allowed for effective risk stratification and exhibited prognostic power in TCGA and GEO sets. The low-risk patients exhibited greater immune infiltration, higher expression of common immune checkpoint factors, and lower scores for tumor immune dysfunction and exclusion.

Conclusion

The PDIS can be used as an effective prognostic model for predicting immunotherapy response to guide clinical decision-making.

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Title: PIK3CA mutation-driven immune signature as a prognostic marker for evaluating the tumor immune microenvironment and therapeutic response in breast cancer
Authors: Xueting Ren
Hanxiao Cui
Luyao Dai
Lidan Chang
Dandan Liu
Wenyu Yan
Xuyan Zhao
Huafeng Kang
Xiaobin Ma
Publication date: 01-03-2024
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Published in: Journal of Cancer Research and Clinical Oncology / Issue 3/2024
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-024-05626-4

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