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Article

RNA Immune Signatures from Pan-Cancer Analysis Are Prognostic for High-Grade Serous Ovarian Cancer and Other Female Cancers

1
Bioinformatics Group, Q2 Solutions - EA Genomics, 5927 S Miami Blvd, Morrisville, NC 27560, USA
2
Division of Gynecologic Oncology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
3
Department of Anatomic Pathology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
4
Department of Gynecology, Charité Medical University of Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
5
Department of Cancer Pharmacology, Levine Cancer Institute, Carolinas Medical Center, 1021 Morehead Medical Drive, Charlotte, NC 28204, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(3), 620; https://doi.org/10.3390/cancers12030620
Received: 11 February 2020 / Revised: 3 March 2020 / Accepted: 5 March 2020 / Published: 7 March 2020
(This article belongs to the Special Issue Preclinical and Clinical Advances in Ovarian Cancer)
Immune cell infiltrates within the tumor microenvironment can influence treatment response and outcome in several cancers. In this study, we developed RNA-based immune signatures from pan-cancer analysis that could serve as potential markers across tumor types and tested them for association with outcome in high-grade serous ovarian cancer (HGSOC) and other female cancers. Pan-cancer RNA-Seq cluster analysis of immune-related gene expression profiles in The Cancer Genome Atlas (TCGA) from 29 different solid tumors (4446 specimens) identified distinct but concordant gene signatures. Among these immune signatures, Cytotoxic Lymphocyte Immune Signature (CLIS), T-cell trafficking (TCT), and the TCT to M2 tumor-associated macrophage (M2TAM) ratio (TCT:M2TAM) were significantly (p < 0.05) associated with overall survival (OS), using multivariable Cox proportional hazards regression models, in a discovery cohort and two independent validation cohorts of HGSOC patients. Notably, the TCT:M2TAM ratio was highly significant (p ≤ 0.000001) in two HGSOC cohorts. Immune signatures were also significant (p < 0.05) in the presence of tumor cytoreduction, BRCA1/2 mutation, and COL2A1 expression. Importantly, the CLIS and TCT signatures were also validated for prognostic significance (p < 0.05) in TCGA cohorts for endometrial and high tumor mutational burden (Hi-TMB) breast cancer. These immune signatures also have the potential for being predictive in other cancers and for patients following different treatment strategies. View Full-Text
Keywords: RNA immune signature; tumor microenvironment; high-grade serous ovarian cancer; survival outcome; multivariable Cox models RNA immune signature; tumor microenvironment; high-grade serous ovarian cancer; survival outcome; multivariable Cox models
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MDPI and ACS Style

Jones, W.D.; Michener, C.M.; Biscotti, C.; Braicu, I.; Sehouli, J.; Ganapathi, M.K.; Ganapathi, R.N. RNA Immune Signatures from Pan-Cancer Analysis Are Prognostic for High-Grade Serous Ovarian Cancer and Other Female Cancers. Cancers 2020, 12, 620. https://doi.org/10.3390/cancers12030620

AMA Style

Jones WD, Michener CM, Biscotti C, Braicu I, Sehouli J, Ganapathi MK, Ganapathi RN. RNA Immune Signatures from Pan-Cancer Analysis Are Prognostic for High-Grade Serous Ovarian Cancer and Other Female Cancers. Cancers. 2020; 12(3):620. https://doi.org/10.3390/cancers12030620

Chicago/Turabian Style

Jones, Wendell D., Chad M. Michener, Charles Biscotti, Iona Braicu, Jalid Sehouli, Mahrukh K. Ganapathi, and Ram N. Ganapathi. 2020. "RNA Immune Signatures from Pan-Cancer Analysis Are Prognostic for High-Grade Serous Ovarian Cancer and Other Female Cancers" Cancers 12, no. 3: 620. https://doi.org/10.3390/cancers12030620

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