Integrated single-cell and bulk RNA sequencing analysis identifies a neoadjuvant chemotherapy-related gene signature for predicting survival and therapy in breast cancer

Abstract

Neoadjuvant chemotherapy (NAC) is a well-established treatment modality for locally advanced breast cancer (BC). However, it can also result in severe toxicities while controlling tumors. Therefore, reliable predictive biomarkers are urgently needed to objectively and accurately predict NAC response. In this study, we integrated single-cell and bulk RNA-seq data to identify nine genes associated with the prognostic response to NAC: NDRG1, CXCL14, HOXB2, NAT1, EVL, FBP1, MAGED2, AR and CIRBP. Furthermore, we constructed a prognostic risk model specifically linked to NAC. The clinical independence and generalizability of this model were effectively demonstrated. Additionally, we explore the underlying cancer hallmarks and microenvironment features of this NAC response-related risk score, and further assess the potential impact of risk score on drug response. In summary, our study constructed and validated a nine-gene signature associated with NAC prognosis, which was accomplished through the integration of single-cell and bulk RNA data. The results of our study are of crucial significance in the prediction of the efficacy of NAC in BC, and may have implications for the clinical management of this disease.

Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer

“…CIRP expression negatively correlated with malignancy in ovarian tumors, endometrial cancers, and nasal cancers [26,27,32,71,72]. A recent study identified CIRP as one of nine genes associated with the prognostic response to neoadjuvant therapy [73]. Our observations support the role for CIRP as a tumor suppressor that reduces the progression and invasive potential of mammary gland tumors and encourages further delineation of the effects and benefits of CIRP on breast (and potentially ovarian and endometrial) cancer development and progression.…”

“…CIRP expression is altered in several cancers, including breast cancer. While the normal physiological role of CIRP as a stress-induced RBP has been well characterized, more recent studies have detailed the roles for CIRP in several diseases, including different forms of cancer and in inflammation [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]32,34,37,38,[40][41][42][70][71][72][73]. Our previous studies identified a role for CIRP in suppressing epithelial proliferation during mammary gland development, specifically at the transition from lactation to involution [28].…”