Research Paper Volume 16, Issue 2 pp 1077—1095
Establishing the role of BRCA1 in the diagnosis, prognosis and immune infiltrates of breast invasive cancer by bioinformatics analysis and experimental validation
- 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
Received: September 8, 2023 Accepted: November 16, 2023 Published: January 13, 2024
https://doi.org/10.18632/aging.205366How to Cite
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 RT-qPCR 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.
Abbreviations
WB: Western blot; BRCA: breast invasive cancer; RT-qPCR: quantitative reverse transcription-polymerase chain reaction; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; OS: overall survival; PFI: progress free interval; ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2; LumB: Luminal B; IDC: infiltrating ductal carcinoma; ILC: infiltrating lobular carcinoma.