Outcome-related differences in gene expression profiles of high-grade serous ovarian cancers following neoadjuvant chemotherapy

David Octeau, Roy Kessous, Kathleen Klein, Liron Kogan, Manuella Pelmus, Alex Ferenczy, Celia M.T. Greenwood, Leon C. Van Kempen, Shannon Salvador, Susie Lau, Patricia N. Tonin, Amber Yasmeen, Walter H. Gotlieb

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Large-scale genomic studies have detailed the molecular landscape of tumors from patients with high-grade serous ovarian cancers (HGSC) who underwent primary debulking surgery and correlated the identified subgroups to survival. In recent years, there is increased use of neoadjuvant chemotherapy (NACT) for patients with HGSC and while abundant data exist for patients who underwent primary debulking, little data are available on the cancer cells remaining after NACT that could lead to recurrences. We aimed to analyze gene expression profiles of NACT-treated HGSC tumor samples, and correlate them to treatment response and outcome. Tumor samples were collected from patients with stage III or IV HGSC (NACT cohort, N = 57) at the time of surgery and diagnosis (biopsy samples N = 8). Tumor content was validated by histologic examination and bioinformatics. Gene expression analysis was performed using a tailored NanoString-based assay, while sequencing was performed using MiSeq. A cross-validated survival classifier revealed patient clusters with either a "Better" or "Worse" prognostic outcome. The association with overall survival remained significant after controlling for clinical variables, and differential gene expression, gene set enrichment analyses, and the appropriate survival models were used to assess the associations between alterations in gene expression in cancer cells remaining after NACT and outcome. Pathway-based analysis of the differentially expressed genes revealed comparatively high levels of cell cycle and DNA repair gene expression in the poor outcome group.

Original languageEnglish
Pages (from-to)2422-2431
Number of pages10
JournalMolecular Cancer Research
Volume17
Issue number12
DOIs
StatePublished - 1 Jan 2019
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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