Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we performed a comprehensive differential analysis of 165 TNBC samples by integrating RNA-seq data of breast tumor tissues and adjacent normal tissues from both our cohort and The Cancer Genome Atlas (TCGA). Pathway enrichment analysis was conducted to evaluate the biological function of TNBC-specific expressed genes. Further multivariate Cox proportional hazard regression was performed to evaluate the effect of these genes on TNBC prognosis. In this report, we identified a total of 148 TNBC-specific expressed genes that were primarily enriched in mammary gland morphogenesis and hormone levels related pathways, suggesting that mammary gland morphogenesis might play a unique role in TNBC patients differing from other breast cancer types. Further survival analysis revealed that nine genes ( FSIP1, ADCY5, FSD1, HMSD, CMTM5, AFF3, CYP2A7, ATP1A2, and C11orf86) were significantly associated with the prognosis of TNBC patients, while three of them ( ADCY5, CYP2A7, and ATP1A2) were involved in the hormone-related pathways. These findings indicated the vital role of the hormone-related genes in TNBC tumorigenesis and may provide some independent prognostic markers as well as novel therapeutic targets for TNBC.

Highlights

  • Breast cancer is the most diagnosed cancer and the leading cause of cancer-related death among females in the world, accounting for 25% of all cancer cases and 15% of all cancer deaths in women[1]

  • Triple negative breast cancer (TNBC) accounts for approximately 15% of all invasive breast cancers and is recognized as an aggressive subgroup as it occurs primarily in young women and has a high potential to metastasize[7]

  • Chemotherapy remains the mainstay of treatment for patients with TNBC for the absence of definite therapeutic targets, so it is of an urgent need to identify potential diagnostic and therapeutic markers such as immunotherapy[20]

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Summary

Introduction

Breast cancer is the most diagnosed cancer and the leading cause of cancer-related death among females in the world, accounting for 25% of all cancer cases and 15% of all cancer deaths in women[1]. Breast cancer is a heterogeneous disease with a variety of diversity in histologic, molecular and biological features[4], affecting the diagnosis and prognosis of breast cancer. Since TNBC holds many aggressive features compared with other subtypes of breast cancer, such as susceptibility in younger women, shorter period to relapse and higher tendency to metastasize to viscera rather than to bone[7,8], there is an urgent need to investigate potential biomarkers in the diagnosis and treatment of TNBC

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