Association of ATP-binding cassette transporter genomic alterations and expressions with patient survival in breast and prostate cancer

ATP结合盒转运蛋白基因组改变和表达与乳腺癌和前列腺癌患者生存率的相关性

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Abstract

ATP-Binding Cassette (ABC) transporters play a key role in drug resistance and cancer progression. We analyzed the correlation between ABC transporter gene alterations and patient survival in breast and prostate cancers using large-scale genomic datasets. DepMap analysis revealed the overall dependency of cancer cell lines on ABC transporter genes such as ABCG2, ABCG1, ABCC4, ABCA2, ABCA3, ABCC2, ABCC3, ABCC6, ABCC7 (CFTR), and ABCC9, with ABCC6 and ABCC7 showing notably high dependence. Data from the cBioPortal for Cancer Genomics, incorporating multiple phase-3 randomized clinical trials, identified genomic alterations including amplifications, deletions, and mutations in breast cancer patients (32 studies, 15,404 samples) and prostate cancer patients (29 studies, 13,857 samples). Kaplan-Meier analysis showed a significant correlation between ABC transporter gene alterations and overall survival in prostate cancer, but not in breast cancer. However, we found reduced relapse-free survival correlating with reduced RNA expression in select ABC transporters in 4929 breast cancer patients in a KMplot analysis. These findings highlight the potential role of ABC transporters in prostate and breast cancer prognosis and warrant further investigation into their therapeutic implications.

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