Affiliation:
1. The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
2. Department of Breast surgery, The Affiliated Lihuili Hospital, Ningbo University
3. Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Abstract
Abstract
Background Targeted therapy plays an important role in the treatment of breast cancer. However, more biomarkers are still needed to distinguish breast cancer subgroups and further achieve precise targeted therapy.Methods This study analyzed the mutation database of breast cancer and found the gene DNAH10 with high mutation frequency and significant impact on prognosis. The differential genes between the DNAH10 mutant group and the wild-type group were further analyzed, and independent prognostic factors were identified from them.Results A prognostic model was established based on CCL8, FLT3, KLHDC7B, DCD, and GBP2 genes. This model divides breast cancer patients into high-risk group and low-risk group, which has a good predictive value for the prognosis of patients. In addition, analysis of tumor immune microenvironment infiltration revealed that memory B cells, CD8 + T cells, monocytes had higher infiltration scores in the low-risk group than in the high-risk group. And both MHC I and MHC II were higher in the low-risk group. It is suggested that the low-risk group may respond better to immunotherapy. Different DNAH10 copy number variants were also associated with tumor immune microenvironment infiltration. It was further verified by in vitro experiments that DNAH10 mutation promoted tumor proliferation, invasion and migration.Conclusion Our predictive model may be an effective tool for precise diagnosis and treatment of breast cancer, helping to select populations susceptible to chemotherapy and immunotherapy.
Publisher
Research Square Platform LLC
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