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Comparison of molecular profile in triple-negative inflammatory and non-inflammatory breast cancer not of mesenchymal stem-like subtype


Autoři: Yohei Funakoshi aff001;  Ying Wang aff004;  Takashi Semba aff001;  Hiroko Masuda aff001;  David Hout aff005;  Naoto T. Ueno aff001;  Xiaoping Wang aff001
Působiště autorů: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America aff001;  Section of Translational Breast Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America aff002;  Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America aff003;  Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America aff004;  Insight Genetics, Inc., Nashville, Tennessee, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222336

Souhrn

Background

Inflammatory breast cancer (IBC) is an aggressive form of breast cancer. The triple-negative subtype of IBC (TN-IBC) is particularly aggressive. Identification of molecular differences between TN-IBC and TN-non-IBC may help clarify the unique clinical behaviors of TN-IBC. However, our previous study comparing gene expression between TN-IBC and TN-non-IBC did not identify any TN-IBC-specific molecular signature. Lehmann et al recently reported that the mesenchymal stem-like (MSL) TNBC subtype consisted of infiltrating tumor-associated stromal cells but not cancer cells. Therefore, we compared the gene expression profiles between TN-IBC and TN-non-IBC patient samples not of the MSL subtype.

Methods

We classified 88 TNBC samples from the World IBC Consortium into subtypes according to the Vanderbilt classification and Insight TNBCtype, removed samples of MSL and unstable subtype, and compared gene expression profiles between the remaining TN-IBC and TN-non-IBC samples.

Results

In the Vanderbilt analysis, we identified 75 genes significantly differentially expressed between TN-IBC and TN-non-IBC at an FDR of 0.2. In the Insight TNBCtype analysis, we identified 81 genes significantly differentially expressed between TN-IBC and TN-non-IBC at an FDR of 0.4. In both analyses, the top canonical pathway was “Fc Receptor-mediated Phagocytosis in Macrophages and Monocytes”, and the top 10 differentially regulated genes included PADI3 and MCTP1, which were up-regulated, and CDC42EP3, SSR1, RSBN1, and ZC3H13, which were downregulated.

Conclusions

Our data suggest that the activity of macrophages might be enhanced in TN-IBC compared with TN-non-IBC. Further clinical and preclinical studies are needed to determine the cross-talk between macrophages and IBC cells.

Klíčová slova:

Biology and life sciences – Genetics – Gene expression – Gene regulation – Small interfering RNAs – Cell biology – Cellular types – Animal cells – Blood cells – White blood cells – Macrophages – Monocytes – Immune cells – Cell processes – Phagocytosis – Biochemistry – Nucleic acids – RNA – Non-coding RNA – Medicine and health sciences – Immunology – Immune response – Inflammation – Oncology – Cancers and neoplasms – Breast tumors – Breast cancer – Diagnostic medicine – Signs and symptoms – Pathology and laboratory medicine


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