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Molecular Cancer Research
Molecular Cancer Research

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Cancer “-omics”

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 and Walter H. Gotlieb
David Octeau
Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Canada.Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada.
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  • ORCID record for David Octeau
Roy Kessous
Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada.
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Kathleen Klein
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
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Liron Kogan
Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada.
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Manuella Pelmus
Division of Pathology, Jewish General Hospital, Montréal, Canada.
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Alex Ferenczy
Division of Pathology, Jewish General Hospital, Montréal, Canada.
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Celia M.T. Greenwood
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.Departments of Medicine and Human Genetics, McGill University, Montreal, Quebec, Canada.
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Leon C. Van Kempen
Department of Molecular Pathology, Jewish General Hospital, Montreal, Canada.
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Shannon Salvador
Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada.
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Susie Lau
Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada.
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Patricia N. Tonin
Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.Departments of Medicine and Human Genetics, McGill University, Montreal, Quebec, Canada.
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Amber Yasmeen
Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada.
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  • For correspondence: amber.yasmeen@mail.mcgill.ca
Walter H. Gotlieb
Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada.
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DOI: 10.1158/1541-7786.MCR-19-0398 Published December 2019
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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.

Implications: Our work suggests mRNA expression patterns in key genes following NACT may reflect response to treatment and outcome in patient with HGSC.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).

  • Mol Cancer Res 2019;17:2422–31

  • Received April 20, 2019.
  • Revision received July 14, 2019.
  • Accepted September 12, 2019.
  • Published first September 17, 2019.
  • ©2019 American Association for Cancer Research.
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Molecular Cancer Research: 17 (12)
December 2019
Volume 17, Issue 12
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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 and Walter H. Gotlieb
Mol Cancer Res December 1 2019 (17) (12) 2422-2431; DOI: 10.1158/1541-7786.MCR-19-0398

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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 and Walter H. Gotlieb
Mol Cancer Res December 1 2019 (17) (12) 2422-2431; DOI: 10.1158/1541-7786.MCR-19-0398
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Molecular Cancer Research
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