Patient-derived cell lines unveil COL1A2 as a predictor of docetaxel resistance in breast cancer
Breast cancer is the most common type of malignant tumour among women globally, with a major cause of cancer-related mortality worldwide. Chemoresistance presents a significant challenge in breast cancer therapy and serves as the primary factor contributing to tumour recurrence and metastasis. At present, there is a paucity of effective predictive strategies in this field. In this study, we successfully established patient-derived primary cancer cell lines (PCCL) from four patients with HR+/HER2- breast cancer (Luminal B, HER2 non-amplified) using primary cell culture technology. The retention of the original tumour's pathological characteristics and drug response heterogeneity was confirmed. The aim was to delve into the mechanisms and predictive models underlying chemotherapy resistance in HR+/HER2- breast cancer. Our investigation revealed varying sensitivities of PCCL to taxanes, including docetaxel. Through RNA sequencing and protein-protein interaction (PPI) network analysis, we discovered that the COL1A2 gene is significantly overexpressed in HR+/HER2- breast cancer patients exhibiting docetaxel resistance. Notably, this overexpression shows a negative correlation with the patients' pathological complete response rate (pCR) and recurrence-free survival (RFS). In functional assays, higher COL1A2 expression correlated with diminished docetaxel sensitivity in HR+/HER2-negative breast cancer cells. These findings are consistent with the imaging assessments and postoperative pathological outcomes of patients who underwent neoadjuvant therapy (AC-T regimen). These findings suggest that COL1A2 is associated with reduced chemotherapy sensitivity in HR+/HER2- breast cancer and may serve as a candidate biomarker to guide neoadjuvant taxane selection. Overall, this study provides a novel theoretical foundation for selecting neoadjuvant chemotherapy drugs for advanced breast cancer patients. Overall design: RNA-seq of human Breast cancer: docetaxel-resistant group and docetaxel-sensitive group