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Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer

Abstract

MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival.

  • Ovarian Neoplasms
  • Cancer
  • Biological Markers
  • Biostatistics
  • Clinical Research

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors PG and AL conceived and designed the experiment. PG, AL and IK wrote the paper. IK performed the analysis, with assistance from AS. JL, AM, JW and LDS performed surgeries and resected tissue. IS and MK recruited and followed up with patients. IS, JP, SL and TB reviewed charts, request tissue blocks and acquired samples for analysis. JP, HK, CP and AL performed the RNA assays. All authors reviewed and approved the final manuscript.

  • Funding This work was supported by Linda and Dr Myron Teitelbaum, the Monter Cancer Center at Northwell Cancer Institute, Moms Who Kick, Manhasset Womens Coalition Against Breast Cancer, Henry Gabbay, and Stand Up 2 Cancer.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval All tumor samples were collected under a protocol approved by the institutional review board (IRB) of Northwell Health. The methods were carried out in accordance with the approved guidelines. All experimental protocols were approved by the Northwell Health IRB

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Expression and clinical data are available on GEO under accession numbers GSE81873 and GSE8177.

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