Establishing the role of BRCA1 in the diagnosis, prognosis and immune infiltrates of breast invasive cancer

Sep 21, 2026

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BRCA1 is a well-known tumor-suppressor gene, yet its link to immune infiltration patterns and patient prognosis in breast invasive cancer has remained insufficiently characterized. A bioinformatics workflow using TCGA expression profiles and clinical data was combined with wet-lab validation to compare BRCA1 expression, assess functional enrichment, analyze DNA methylation, evaluate survival associations with Cox and Kaplan-Meier methods, and build a prognostic nomogram. Immune cell infiltration was quantified via ssGSEA.

LanguageEnglish

CategoryResearch & Report

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Pages19

Reading Time48 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

[www.aging-us.com](www.aging-us.com) AGING 2024, Vol. 16, No. 2 Research Paper Establishing the role of BRCA1 in the diagnosis, prognosis and immune infiltrates of breast invasive cancer by bioinformatics analysis and experimental validation Leilei Li1,*, Shuangyan Li2,*, Xuyang Zhang3,*, Liying Mei4, Xueqin Fu4, Min Dai4, Na Wei4 1 Department of Pathology, Kunming Medical University, Kunming 650500, Yunnan, China 2 Department of Oncology, Kunming Medical University, Kunming 650500, Yunnan, China 3 Department of Hepatobiliary, Second Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China 4 Department of Breast Surgery, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou, China *Equal contribution Correspondence to: Min Dai, Na Wei; email: [skydine@sina.com](skydine@sina.com), [https://orcid.org/0000-0001-8325-568X](https://orcid.org/0000-0001-8325-568X); [xtlp77@163.com](xtlp77@163.com), [https://orcid.org/0009-0003-6422-3748](https://orcid.org/0009-0003-6422-3748) Keywords: breast invasive cancer, breast cancer susceptibility gene 1, prognosis, immune cells, methylation Received: September 8, 2023 Accepted: November 16, 2023 Published: January 13, 2024 Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Background: Breast cancer susceptibility gene 1 (BRCA1) is a well-known gene that acts a vital role in suppressing the growth of tumors. Previous studies have primarily focused on the genetic mutations of BRCA1 and its association with hereditary breast invasive carcinoma (BRCA). However, little research has been done to investigate the relationship between BRCA1 and immune infiltrates and prognosis in BRCA. Methods: We obtained the expression profiles and clinical information of patients with BRCA from the Cancer Genome Atlas (TCGA) database. The levels of the BRCA1 gene between BRCA tissues and normal breast tissues were compared through the Wilcoxon rank-sum test. Additionally, we performed WB and RTqPCR techniques to detect the expression of BRCA1 . We conducted functional enrichment analyses. Furthermore, we assessed immune cell infiltration using a single-sample gene set enrichment analysis. The methylation status of the BRCA1 gene was analyzed using the UALCAN and MethSurv databases. The Cox regression analysis and (KM) Kaplan-Meier method were employed to determine the prognostic value of BRCA1 . In order to provide a practical tool for predicting the overall survival rates at different time points, we also constructed a nomogram. Results: Our analysis revealed that the expression of BRCA1 was significantly higher in BRCA tissues compared to normal tissues. Furthermore, this increased level of BRCA1 was found to be associated with specific BRCA subtypes, including T2, stage II, ER positive, ect. Importantly, the overexpression of BRCA1 was shown to be a negative prognostic marker for the overall survival rates of BRCA patients. Moreover, low methylation status of the BRCA1 gene was related to a poorer prognosis. Furthermore, our results indicated that high levels of BRCA1 are related to a decrease in level of killer immune cells, such as natural killer (NK) cells, macrophages, CD8+ T cells, and plasma-like dendritic cells (pDCs) within the tumor microenvironment. Conclusions: Our study is the first to provide evidence indicating that the presence of BRCA1 can serve as a reliable marker for both diagnosing and determining the prognosis of BRCA. Moreover, BRCA1 acts as a crucial indicator of the cancer’s potential to infiltrate and invade the immune system, which has important implications for developing targeted therapies in BRCA. INTRODUCTION Breast invasive cancer (BRCA) is the most common malignant tumor in women across th

FAQs

How was BRCA1 expression compared between breast invasive cancer and normal tissues?

BRCA expression profiles and clinical information were taken from TCGA. BRCA1 expression levels in cancer versus normal tissues were compared using the Wilcoxon rank-sum test, and expression was validated with WB and RT-qPCR.

What prognostic relationships were reported for BRCA1?

Higher BRCA1 expression was associated with worse overall survival in breast invasive cancer patients. Lower BRCA1 methylation status was also linked to a poorer prognosis, and Cox regression plus Kaplan-Meier analyses were used to support these findings.

How did BRCA1 relate to immune infiltration in the tumor microenvironment?

Immune infiltration was evaluated using ssGSEA. The study found that increased BRCA1 expression corresponded to decreased levels of killer immune cells, including NK cells, macrophages, CD8+ T cells, and pDCs.

Sep 21, 2026

Uploaded by Patrick