Analysis of the Effect of SNAI Family in Breast Cancer and Immune Cell

Yifei Tu; Pengfei Fang; Long Zhang; Kewang Sun

doi:10.3389/fcell.2022.906885

Analysis of the Effect of SNAI Family in Breast Cancer and Immune Cell

Front Cell Dev Biol. 2022 Jul 8:10:906885. doi: 10.3389/fcell.2022.906885. eCollection 2022.

Authors

Yifei Tu¹, Pengfei Fang¹, Long Zhang¹, Kewang Sun²

Affiliations

¹ MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China.
² General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.

Abstract

SNAI family members are transcriptional repressors that induce epithelial-mesenchymal transition during biological development. SNAIs both have tumor-promoting and tumor-inhibiting effect. There are key regulatory effects on tumor onset and development, and patient prognosis in infiltrations of immune cell and tumor microenvironmental changes. However, the relationships between SNAIs and immune cell infiltration remain unclear. We comprehensively analyzed the roles of SNAIs in cancer. We used Oncomine and TCGA data to analyze pan-cancer SNAI transcript levels. By analyzing UALCAN data, we found correlations between SNAI transcript levels and breast cancer patient characteristics. Kaplan-Meier plotter analysis revealed that SNAI1 and SNAI2 have a bad prognosis, whereas SNAI3 is the opposite. Analysis using the cBio Cancer Genomics Portal revealed alterations in SNAIs in breast cancer subtypes. Gene Ontology analysis and gene set enrichment analysis were used to analyze differentially expressed genes related to SNAI proteins in breast cancer. We used TIMER to analyze the effects of SNAI transcript levels, mutations, methylation levels, and gene copy number in the infiltration of immune cell. Further, we found the relationships between immune cell infiltration, SNAI expression levels, and patient outcomes. To explore how SNAI proteins affect immune cell, we further studied the correlations between immunomodulator expression, chemokine expression, and SNAI expression. The results showed that SNAI protein levels were correlated with the expression of several immunomodulators and chemokines. Through analysis of PharmacoDB data, we identified antitumor drugs related to SNAI family members and analyzed their IC50 effects on various breast cancer cell lines. In summary, our study revealed that SNAI family members regulate different immune cells infiltrations by gene copy number, mutation, methylation, and expression level. SNAI3 and SNIA1/2 have opposite regulatory effects. They all play a key role in tumor development and immune cell infiltration, and can provide a potential target for drug therapy.

Keywords: SNAI; breast cancer; drug; immune cell; immunomodulator; methylation.