Identification of immune-related biomarkers for predicting neoadjuvant chemotherapy sensitivity in HER2 negative breast cancer via bioinformatics analysis

Background: Neoadjuvant chemotherapy (NAC) is an important treatment for breast cancer (BC) patients. However, due to the lack of specific therapeutic targets, only 1/3 of human epidermal growth factor receptor 2 (HER2)-negative patients reach pathological complete response (pCR). Therefore, there is an urgent need to identify novel biomarkers to distinguish and predict NAC sensitive in BC patients. Methods: The GSE163882 dataset, containing 159 BC patients treated with NAC, was downloaded from the Gene Expression Omnibus (GEO) database. Patients with pathological complete response (pCR) and those with residual disease (RD) were compared to obtain the differentially expressed genes (DEGs). Functional enrichment analyses were conducted on these DEGs. Then, we intersect the DEGs and immune-related genes to obtain the hub immune biomarkers, and then use the linear fitting model ("glm" package) to construct a prediction model composed of 9 immune biomarkers. Finally, the single sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze immune cell invasion in BC patients, and the correlation between immune cell content and immune gene expression levels was analyzed. Results: Nine immune-related biomarkers were obtained in the intersection of DEGs and immune-related genes. Compared with RD patients, CXCL9, CXCL10, CXCL11, CXCL13, GZMB, IDO1, and LYZ were highly expressed in pCR patients, while CXCL14 and ESR1 were lowly expressed in pCR patients. After linear fitting of the multi-gene expression model, the area under the curve (AUC) value of the ROC curve diagnosis of pCR patients was 0.844. Immunoinfiltration analysis showed that compared with RD patients, 15 of the 28 immune cell types examined showed high-infiltration in pCR patients, including activated CD8 T cells, effector memory CD8 T cells, and activated CD4 T cells. Conclusions: This investigation ultimately identified 9 immune-related biomarkers as potential tools for assessing the sensitivity of NAC in HER2-negative BC patients. These biomarkers have great potential for predicting pCR BC patients.