Patient-derived cell lines unveil COL1A2 as a predictor of docetaxel resistance in breast cancer

Breast cancer is the most common malignant tumor among women worldwide and a major cause of cancer-related mortality. Chemoresistance presents a significant challenge in breast cancer therapy and is a primary driver of tumor recurrence and metastasis. However, effective predictive strategies for chemoresistance remain limited. This study aimed to investigate the mechanisms and predictive models underlying chemotherapy resistance in HR+/HER2- breast cancer.

Patient-derived primary cancer cell lines (PCCLs) were successfully established from four patients with HR+/HER2- breast cancer (Luminal B, HER2 non-amplified) using primary cell culture techniques. The retention of the original tumors' pathological characteristics and drug response heterogeneity was confirmed. The sensitivities of PCCLs to taxanes, including docetaxel, were evaluated. RNA sequencing followed by protein-protein interaction (PPI) network analysis was performed to identify candidate genes associated with docetaxel resistance. The expression of COL1A2 was then correlated with pathological complete response (pCR) and recurrence-free survival (RFS) in patients who received neoadjuvant chemotherapy (AC-T regimen). Functional assays were conducted to assess the impact of COL1A2 expression on docetaxel sensitivity in HR+/HER2- breast cancer cells.

PCCLs derived from HR+/HER2- breast cancer exhibited heterogeneous sensitivity to taxanes, including docetaxel. RNA sequencing and PPI network analysis identified COL1A2 as significantly overexpressed in HR+/HER2- breast cancer patients with docetaxel resistance. Elevated COL1A2 expression showed a negative correlation with pCR rates and RFS. In functional assays, higher COL1A2 expression was associated with reduced sensitivity to docetaxel in HR+/HER2- breast cancer cells. These findings were consistent with imaging assessments and postoperative pathological outcomes in patients who underwent neoadjuvant AC-T therapy.

Our findings indicate 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. This study provides a novel theoretical basis for optimizing neoadjuvant chemotherapy regimens in patients with advanced HR+/HER2- breast cancer.