Investigation of Candidate Genes and Pathways in Basal/TNBC Patients by Integrated Analysis

Abstract

Purpose: This study aims to identify the key pathway and related genes and to further explore the potential molecular mechanisms of triple negative breast cancer (TNBC). Methods: The transcriptome data and clinical information of breast cancer patients were downloaded from the TCGA database, including 94 cases of paracancerous tissue, 225 cases of Basal like type, 151 cases of Her2 type, 318 cases of Luminal type A, 281 cases of Luminal type B, and 89 cases of Normal Like type. The differentially expressed genes (DEGs) were identified based on the criteria of |logFC|≥1.5 and adjust P < 0.001.Their functions were annotated by gene ontology (GO) analysis and Kyoto Encyclopedia of differentially expressed genes & Genomes (KEGG) pathway analysis. Cox regression univariate analysis and Kaplan-Meier survival curves (Log-rank method) were used for survival analysis. FOXD1, DLL3 and LY6D were silenced in breast cancer cell lines, and cell viability was assessed by CCK-8 assay. Further, the expression of FOXD1, DLL3 and LY6D were explored by immunohistochemistry on triple negative breast tumor tissue and normal breast tissue. Results: A total of 533 DEGs were identified. Functional annotation showed that DEGs were significantly enriched in intermediate filament cytoskeleton, DNA−binding transcription activator activity, epidermis development, and Neuroactive ligand−receptor interaction. Survival analysis found that FOXD1, DLL3, and LY6D showed significant correlation with the prognosis of patients with the Basal-like type ( P < 0.05). CCK-8 assay showed that compared with Doxorubicin alone group, the cytotoxicity of Doxorubicin combined with siRNA-knockdown of FOXD1, DLL3, or LY6D was much significant. Conclusion: The DEGs and their enriched functions and pathways identified in this study contribute to the understanding of the molecular mechanisms of TNBC. In addition, FOXD1, DLL3, and LY6D may be defined as the prognostic markers and potential therapeutic targets for TNBC patients.

The potential mechanism of HIF-1α and CD147 in the development of triple-negative breast cancer

“…TNBC is a highly invasive malignant tumor, and its prognosis is worse than other subtypes of breast cancer. [ 15 ] Although TNBC is sensitive to chemotherapy, patients have limited benefit from it. [ 16 ] The main reason is that the tumor has strong drug resistance and obvious side effects of chemotherapy, and it is easy to relapse and metastasize.…”

GEMIN4, a potential therapeutic targets for patients with basal-like subtype breast cancer

“…WGCNA identified multiple candidate genes associated with BLBC and those genes were enriched in cornification, epidermis development, epithelial cell differentiation, estrogen signaling pathway, and pathways in cancer, which is consistent with the pathogenesis of BLBC. For example, the DEGs of triple negative breast cancer were also enriched in epidermis development according to the previous research [ 17 ]. In addition, some transcription factors essential for mammary luminal epithelial cell differentiation are also involved in the BLBC and estrogen receptor downstream target gene could inhibit the proliferation as well as migration of BC cells [ 18 , 19 ].…”

Development and Validation of a Risk Prediction Model for Breast Cancer Prognosis Based on Depression-Related Genes

“…In addition, PXDNL and FOXD1 were reportedly involved in breast cancer pathogenesis and were significant in predicting prognosis. FOXD1 was found to be significantly related to the prognosis of basal-like breast cancer ( 32 ). Zhao et al ( 33 ) demonstrated that FOXD1 could increase cell proliferation and enhance chemoresistance of cancer cells by targeting p27.…”