No 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.

Paclitaxel is one of the most effective chemotherapy drugs for breast cancer worldwide but 20-30% patients show primary resistance to the drug. Screening and identification of markers that facilitate effective and rapid prediction of sensitivity to paclitaxel is therefore an urgent medical requirement. In the present study, G protein signaling modulator 2 (GPSM2) mRNA levels were significantly associated with taxane sensitivity in experiments based on the Gene Expression Omnibus (GEO) online database. Immunohistochemical analysis consistently revealed a significant association of GPSM2 protein levels with paclitaxel sensitivity in breast cancer patients. Knockdown of GPSM2 reduced the sensitivity of breast cancer cells to paclitaxel via regulation of the cell cycle. Animal experiments further corroborated our in vitro findings. These results suggest that GPSM2 plays an important role in breast cancer resistance, supporting its utility as a potential target for improving drug susceptibility in patients as well as a marker of paclitaxel sensitivity.

Gastric cancer (GC) was the fifth most common cancer and the fourth leading cause of cancer-related deaths worldwide in 2020. 1 In 2010-2014, the 5-year-survival was very high in Korea (69%) and Japan (60%), but in China, it was only 35.9%, 2 where initial asymptomatic development and subsequent nonspecific symptoms result in a diagnosis at advanced stages with a poor prognosis. Assuming that the current incidence rates remain the same, the annual number of new GC cases are predicted to increase from 1.09 million cases to 1.77 million cases by 2040. 3 Helicobacter pylori is an important GC risk factor. 4 The Correa model 5 demonstrates the progression of human gastric carcinogenesis from the normal gastric mucosa to cancer. Persistent H. pylori