A four‐gene signature predicts the efficacy of paclitaxel‐based neoadjuvant therapy in human epidermal growth factor receptor 2–negative breast cancer

Abstract

Neoadjuvant chemotherapy (NAC) is the major preoperative treatment of breast cancer (BC) with negative human epidermal growth factor receptor 2 (HER2), and the efficacy of NAC and the optimization of regimen are under intensive research. The current study aimed to define the predictive biomarkers for paclitaxel (PTX) response in NAC of HER2‐negative BC. Data from GSE25065, GSE26065, GSE41998, as well as drug sensitivity data of breast and ovarian cancer cell line from NCI60, were used. Through logistic regression, COX regression, and correlation analysis with bootstrapping, we found that four genes (CDK8, FAM64A, MARC2, and OCEL1) were associated with drug sensitivity of PTX. The four gene “≥3” model had the best classification accuracy. Subgroup analysis found that the model performed well in the hormone receptor positive, HER2‐negative subgroup and did not perform well in the triple‐negative subgroup. Decision curve analysis showed that the model could enhance the predictive effect of clinical features. Subsequent gene set enrichment analysis, network analysis showed that these genes may be related to the cell cycle, mitosis and other pathways. The current study demonstrated the promising potential of the novel four‐gene signature as a predictive biomarker for pathological complete response of HER2‐negative BC patients and indicated the drug sensitivity of PTX.

RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes

“…Rixen and coworkers recently showed that MARC2 KO mice had decreased levels of total cholesterol and increased glucose levels, suggesting that MARC2 affects energy pathways [36]. However, Li et al showed that reduced MARC2 expression was associated with an increased sensitivity to paclitaxel-based neoadjuvant therapy in human EGFR-2-negative breast cancer patients [37] but, to the best of our knowledge, there have been no previous reports on a role of MARC2 in RCC.…”

<p>Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis</p>

“…17 Importantly, Li et al found that CDK8 was associated with sensitivity of PTX in NCI60 cells. 18 But the interaction among circ_0006528, miR-1299 and CDK8 in breast cancer remains unknown. This study aimed to explore the function of circ_0006528 in PTX resistance of breast cancer, and clarify the potential mechanism of circ_0006528 in PTXresistant breast cancer.…”

Identification of immune-related therapeutically relevant biomarkers in breast cancer and breast cancer stem cells by transcription-wide analysis: a clinical prospective study

“…To be noted, NF-κB activation was proven to be involved in the tumor associated macrophages-mediated tumor growth in human pancreatic ductal adenocarcinoma [29]. PIMREG is known to positively regulate STAT3 activity to promote cell differentiation and shown to be associated with poor survival in the BC and pancreatic cancer [29][30][31][32]. It has been proven that both anti-and proinflammatory cytokines signal through associated receptor/JAK complexes and result in the phosphorylation of STAT3 [33].…”