Cargando…

BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma

BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in...

Descripción completa

Detalles Bibliográficos
Autores principales: Jin, Tong Yi, Park, Kyoung Sik, Nam, Sang Eun, Yoo, Young Bum, Park, Won Seo, Yun, Ik Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998777/
https://www.ncbi.nlm.nih.gov/pubmed/35409110
http://dx.doi.org/10.3390/ijms23073754
_version_ 1784685024670384128
author Jin, Tong Yi
Park, Kyoung Sik
Nam, Sang Eun
Yoo, Young Bum
Park, Won Seo
Yun, Ik Jin
author_facet Jin, Tong Yi
Park, Kyoung Sik
Nam, Sang Eun
Yoo, Young Bum
Park, Won Seo
Yun, Ik Jin
author_sort Jin, Tong Yi
collection PubMed
description BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan–Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.
format Online
Article
Text
id pubmed-8998777
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89987772022-04-12 BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma Jin, Tong Yi Park, Kyoung Sik Nam, Sang Eun Yoo, Young Bum Park, Won Seo Yun, Ik Jin Int J Mol Sci Article BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan–Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted. MDPI 2022-03-29 /pmc/articles/PMC8998777/ /pubmed/35409110 http://dx.doi.org/10.3390/ijms23073754 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jin, Tong Yi
Park, Kyoung Sik
Nam, Sang Eun
Yoo, Young Bum
Park, Won Seo
Yun, Ik Jin
BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma
title BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma
title_full BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma
title_fullStr BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma
title_full_unstemmed BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma
title_short BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma
title_sort brca1/2 serves as a biomarker for poor prognosis in breast carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998777/
https://www.ncbi.nlm.nih.gov/pubmed/35409110
http://dx.doi.org/10.3390/ijms23073754
work_keys_str_mv AT jintongyi brca12servesasabiomarkerforpoorprognosisinbreastcarcinoma
AT parkkyoungsik brca12servesasabiomarkerforpoorprognosisinbreastcarcinoma
AT namsangeun brca12servesasabiomarkerforpoorprognosisinbreastcarcinoma
AT yooyoungbum brca12servesasabiomarkerforpoorprognosisinbreastcarcinoma
AT parkwonseo brca12servesasabiomarkerforpoorprognosisinbreastcarcinoma
AT yunikjin brca12servesasabiomarkerforpoorprognosisinbreastcarcinoma