Heterogeneity of luminal A and HER2-positive breast cancer based on DIA quantitative proteomics and bioinformatics analysis techniques

Abstract

Background: Breast cancer has common tumor biological characteristics, but different characteristics also exist among different subtypes. Different treatment strategies have been adopted for different subtypes at present, but there are still many problems. Thus, an-depth study on the heterogeneity of different types of breast cancer will help to identify new diagnostic therapeutic targets and solve the existing problems of individualized treatment for breast cancer.Methods: In this study proteins of HER2-positive breast cancer, luminal A breast cancer, and para-cancer tissues were quantified based on data independent acquisition (DIA) proteomics technology, and the differentially expressed proteins (DEPs) were screened and analyzed by IPA software and the database among the luminal A (LA ) versus para-cancer tissues (PT) and HER2 versus LA groups.Results: There were 264 up- and 123 down-regulated proteins in the LA versus PT groups. PD-1 and PD-L1 cancer immunotherapy pathways were significantly inhibited, and XBP1 was predicted to be the strongest activator. MTOR was predicted to be the strongest inhibitor. The DEPs were significantly associated with “Cancer” and “Organismal Injury and Abnormalities.” There were 134 up- and 286 down-regulated proteins in the HER2 versus LA groups. Signaling by rho family GTPases was significantly inhibited. XBP1 was predicted to be the strongest activator. TGFB1 was predicted to be the strongest inhibitor. The DEPs were significantly associated with “Cancer,” “Endocrine System Disorders,” and “Organismal Injury and Abnormalities.”Conclusion: Luminal A breast cancer may be insensitive to PD-1 and PD-L1 inhibitors. Signaling by rho family GTPases and RhoGDI signaling play a unique role in the proliferation and metastasis of luminal A and HER2-positive breast cancer, respectively. XBP1 is a promising new target for the treatment of breast cancer, and TGFB1 may play different biological roles in HER2-positive and luminal A breast cancer.