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Integrating Genomic Information with Tumor-Immune Microenvironment in Triple-Negative Breast Cancer

Author

Listed:
  • David Otohinoyi

    (Department of Genetics, Bioinformatics and Genomics (Big) Program, School of Medicine, Louisiana State University Health Sciences Center, 533 Bolivar, New Orleans, LA 70112, USA)

  • Aditi Kuchi

    (Department of Genetics, Bioinformatics and Genomics (Big) Program, School of Medicine, Louisiana State University Health Sciences Center, 533 Bolivar, New Orleans, LA 70112, USA)

  • Jiande Wu

    (Department of Genetics, Bioinformatics and Genomics (Big) Program, School of Medicine, Louisiana State University Health Sciences Center, 533 Bolivar, New Orleans, LA 70112, USA)

  • Chindo Hicks

    (Department of Genetics, Bioinformatics and Genomics (Big) Program, School of Medicine, Louisiana State University Health Sciences Center, 533 Bolivar, New Orleans, LA 70112, USA)

Abstract

Background: the development and progression of triple-negative breast cancer (TNBC) is driven by somatic driver mutations and the tumor-immune microenvironment. To date, data on somatic mutations has not been leveraged and integrated with information on the immune microenvironment to elucidate the possible oncogenic interactions and their potential effects on clinical outcomes. Here, we investigated possible oncogenic interactions between somatic mutations and the tumor-immune microenvironment, and their correlation with patient survival in TNBC. Methods: We performed analysis combining data on 7,875 somatic mutated genes with information on 1,751 immune-modulated genes, using gene-expression data as the intermediate phenotype, and correlated the resulting information with survival. We conducted functional analysis to identify immune-modulated molecular networks and signaling pathways enriched for somatic mutations likely to drive clinical outcomes. Results: We discovered differences in somatic mutation profiles between patients who died and those who survived, and a signature of somatic mutated immune-modulated genes transcriptionally associated with TNBC, predictive of survival. In addition, we discovered immune-modulated molecular networks and signaling pathways enriched for somatic mutations. Conclusions: The investigation revealed possible oncogenic interactions between somatic mutations and the tumor-immune microenvironment in TNBC, likely to affect clinical outcomes.

Suggested Citation

  • David Otohinoyi & Aditi Kuchi & Jiande Wu & Chindo Hicks, 2022. "Integrating Genomic Information with Tumor-Immune Microenvironment in Triple-Negative Breast Cancer," IJERPH, MDPI, vol. 19(21), pages 1-20, October.
    • Handle: RePEc:gam:jijerp:v:19:y:2022:i:21:p:13901-:d:953437
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    References listed on IDEAS

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    1. Sohrab P. Shah & Andrew Roth & Rodrigo Goya & Arusha Oloumi & Gavin Ha & Yongjun Zhao & Gulisa Turashvili & Jiarui Ding & Kane Tse & Gholamreza Haffari & Ali Bashashati & Leah M. Prentice & Jaswinder , 2012. "The clonal and mutational evolution spectrum of primary triple-negative breast cancers," Nature, Nature, vol. 486(7403), pages 395-399, June.
    2. Jiande Wu & Tarun Karthik Kumar Mamidi & Lu Zhang & Chindo Hicks, 2019. "Integrating Germline and Somatic Mutation Information for the Discovery of Biomarkers in Triple-Negative Breast Cancer," IJERPH, MDPI, vol. 16(6), pages 1-16, March.
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