Bioinformatics identification and validation of aging‑related molecular subtype and prognostic signature in breast cancer

Abstract

Patients with metastatic breast cancer have a poor clinical outcome, accounting for more than 90 percent of breast cancer-related deaths. Aging could regulate many biological processes in malignancies by regulating cell senescence. The role of aging has not been fully clarified. Consensus cluster analysis was performed to differentiate The Cancer Genome Atlas (TCGA) breast cancer cases. Least absolute shrinkage and selection operator (LASSO) cox regression analysis was performed to construct an aging-related prognostic signature. A total of 118 differentially expressed aging-related genes (ARGs) was obtained in breast cancer. Consensus clustering analysis identified 3 categories of TCGA-breast cancer with significant difference in prognosis and immune infiltration. We also constructed an aging-related prognostic signature for breast cancer, which had a good performance in predicting the 1-year, 3-year and 5-year OS and disease specific survival (DSS) of breast cancer patients. Further single gene analysis revealed that the expression of PIK3R1 was significantly different in different pT and pN stages of breast cancer. Moreover, low expression of PIK3R1 showed resistance to many drugs based on the data of Genomics of Drug Sensitivity in Cancer (GDSC) and Genomics of Therapeutics Response Portal (CTRP). PIK3R1 played a vital role in many well-known cancer-related pathways. The current study identified 3 clusters of TCGA-breast cancer cases with significant differences in prognosis and immune infiltration. We also constructed an aging-related prognostic signature for breast cancer. However, further in vivo and in vitro studies should be conducted to verify these results.