Predicting The Curative Effect Of Neoadjuvant Chemotherapy With Multiple Pathways Genes In Breast Cancer

Breast cancer is one of the most common malignancies, the incidence of which leads first among females. Recently, neoadjuvant chemotherapy has drawn significant attention by the public, which has been a new treatment for patients with early or/and locally advanced breast cancer in clinic. Neoadjuvant chemotherapy can reduce the size of the primary tumor, thus enabling a substantial fraction of patients with advanced tumors previously considered unresectable to be operable. In addition, this treatment allows patients to become eligible for breast conserving surgery to avoid mastectomy. Nevertheless, not all patients benefit from neoadjuvant chemotherapy. Developing predictive factors for neoadjuvant chemotherapy response would therefore be of great value to patients.All of the pre-chemotherapy samples were collected from the tumor bank constructed at Zhejiang Cancer Hospital, including 15 pathological complete response samples and 17 non-pathological complete response samples. Firstly, we mixed 3 pCR samples and 3 NpCR samples and built cDNA library for the next generation sequencing. 715 differentially-expressed genes were finally detected. Gene Ontology(GO) was then adopted to confirm whether differentially-expressed genes were associated with cellular component, molecular function, catalytic activity and biological processes. After mapping to Kyoto Encyclopedia of Genes and Genomes(KEGG), the included 9 genes of different expression in ubiquitin proteasome pathway and cytokine-cytokine receptor interaction were well-selected(PSMB10, UBD, UBE2 C, and UBE2 S in ubiquitin proteasome pathway, CCL2, CCR1, CXCL10, CXCL11 and IL2 RG in cytokine-cytokine receptor interaction, respectively). The 9 genes were finally quantified by quantitative real-time PCR(qRT-PCR) to validate whether they were differentially expressed. The results of real-time PCR showed that the 9 gene were significantly overexpressed in the pCR patients compared with the NpCR patients. In addition, we established logistic regression equation to predict the curative effect of neoadjuvant chemotherapy. Finally, we found that the breast cancers who PSMB10, UBD, UBE2 C, CXCL10, CXCL11, IL2 RG genes were overexpression had a long months survival and months disease free.In conclusion, we speculated the patients who PSMB10, UBD, UBE2 C, UBE2 S, CCL2, CCR1, CXCL10, CXCL11, IL2 RG genes were overexpression were sensitive to neoadjuvant chemotherapy. Our results will provide a potential clinical application in the future.