Prognostic values of SNAI family members in breast cancer patients

Abstract

Background: Breast cancer (BC) is one of the most lethal malignant tumors and the leading cause of cancer-related death worldwide. Although early diagnostic techniques for BC have been well developed, 40% of cases are still diagnosed at the advanced stage, while for BC patients with distant metastases, the 5-year survival rate is usually lower than 30%. The Snail family, generally regarded as transcriptional repressors, has been indicated to be an essential prognostic factor in malignant tumors. However, limited data exist on public databases concerning the prognostic value of individual Snail family members in BC, especially SNAI3.

Methods: Data from public databases including cBioPortal for Cancer Genomics, Gene Expression Omnibus, UCSC Xena Browser, and Human Protein Atlas (HPA) were downloaded. Based on the Kaplan¬-Meier plotter platform, correlation of the three members of the Snail family and prognosis in BC were analyzed. Individual Snail family members and their co-expressed genes were respectively enriched on different pathways and biological processes via the functional enrichment analysis (FunRich) tool.

Results: High SNAI1 mRNA expression was associated with shorter distant metastasis-free survival (DMFS) in all BC patients regardless of PAM50 subtype. Conversely, high SNAI3 mRNA expression was associated with longer DMFS. Although the presence of SNAI2 expression was significantly associated with DMFS in the whole cohort, no significant correlation was found in patients with luminal A or HER2 subtype. For patients with the most diverse clinicopathological features, high SNAI1 expression was associated with poor survival, with the converse being true for SNAI3. However, the impact on prognosis of patients with different clinicopathological features produced by SNAI2 expression was inconclusive. Furthermore, we discovered that SNAI1 or SNAI2 and their co-expressed genes frequently enriched receptor tyrosine kinase (RTK) signaling and integrin-related pathways which mainly functioned on epithelial-mesenchymal transition and were further involved in several processes of signal transduction and cell communication. Furthermore, as SNAI3, along with its co-expressed genes, enriched immune-related pathways, it may thus play a role in mediating the immune system.

Conclusions: Our analysis revealed that SNAI1 mRNA expression may potentially be a negative prognostic factor, whereas SNAI3 mRNA was associated with positive prognosis in BC. Therefore, the assessment of SNAI1 and SNAI3 expression may be valuable for predicting prognosis in BC patients.

Keywords: Breast cancer (BC); SNAI family; mRNA; prognosis.

Figure 1

Alternation of SNAI family members. (A) Different alternation frequency of the SNAI family members in solid tumors; (B) genetic alternation of SNAI genes in BC; (C) hotspot mutation of SNAI genes; copy number (D) and mRNA expression level (E) of SNAI genes in BC subtypes based on PAM50.

Figure 2

Influence of three SNAI mRNA expression patterns on distant metastasis-free survival. (A) SNAI1, (B) SNAI2, (C) SNAI3.

Figure 3

Distant metastasis-free survival analysis of diverse SNAI mRNA expression patterns in different subtypes of BC. (A,B,C,D) SNAI1, (E,F,G,H) SNAI2, (I,J,K,L) SNAI3.

Figure 4

Pathway and biological process analyses of different SNAI genes and their co-expressed genes. (A,B) SNAI1, (C,D) SNAI2, (E,F) SNAI3.

Figure S1

Expression of SNAI family members. (A) mRNA expression level in normal tissue; (B) protein expression level in solid tumors.

Figure S2

Influence of three SNAI mRNA expression patterns on relapse-free survival (A,B,C) and overall survival (D,E,F). SNAI1, A and D; SNAI2, B and E; SNAI3, C and F.