Identification of a Novel Gene Signature with DDR and EMT Difunctionalities for Predicting Prognosis, Immune Activity, and Drug Response in Breast Cancer

Pan Zhang, Quan Li, Yuni Zhang, Qianqian Wang, Junfang Yan, Aihua Shen and Burong Hu ()
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Pan Zhang: Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China
Quan Li: Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China
Yuni Zhang: Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China
Qianqian Wang: Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China
Junfang Yan: Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China
Aihua Shen: Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China
Burong Hu: Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China

IJERPH, 2023, vol. 20, issue 2, 1-16

Abstract: Breast cancer, with an overall poor clinical prognosis, is one of the most heterogeneous cancers. DNA damage repair (DDR) and epithelial–mesenchymal transition (EMT) have been identified to be associated with cancer’s progression. Our study aimed to explore whether genes with both functions play a more crucial role in the prognosis, immune, and therapy response of breast cancer patients. Based on the Cancer Genome Atlas (TCGA) cancer database, we used LASSO regression analysis to identify the six prognostic-related genes with both DDR and EMT functions, including TP63 , YWHAZ , BRCA1 , CCND2 , YWHAG , and HIPK2 . Based on the six genes, we defined the risk scores of the patients and reasonably analyzed the overall survival rate between the patients with the different risk scores. We found that overall survival in higher-risk-score patients was lower than in lower-risk-score patients. Subsequently, further GO and KEGG analyses for patients revealed that the levels of immune infiltration varied for patients with high and low risk scores, and the high-risk-score patients had lower immune infiltration’s levels and were insensitive to treatment with chemotherapeutic agents. Furthermore, the Gene Expression Omnibus (GEO) database validated our findings. Our data suggest that TP63 , YWHAZ , BRCA1 , CCND2 , YWHAG , and HIPK2 can be potential genetic markers of prognostic assessment, immune infiltration and chemotherapeutic drug sensitivity in breast cancer patients.

Keywords: breast cancer; gene signature; cancer prognostic model; DNA damage repair (DDR); epithelial–mesenchymal transition (EMT) (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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