Multi-gene expression predictors of single drug responses to adjuvant chemotherapy in ovarian carcinoma: predicting platinum resistance.

PloS One
J Stuart FerrissJae K Lee

Abstract

Despite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy. Standard therapy includes treatment with platinum-based combination chemotherapies yet there is no biomarker model to predict their responses to these agents. We here have developed and independently tested our multi-gene molecular predictors for forecasting patients' responses to individual drugs on a cohort of 55 ovarian cancer patients. To independently validate these molecular predictors, we performed microarray profiling on FFPE tumor samples of 55 ovarian cancer patients (UVA-55) treated with platinum-based adjuvant chemotherapy. Genome-wide chemosensitivity biomarkers were initially discovered from the in vitro drug activities and genomic expression data for carboplatin and paclitaxel, respectively. Multivariate predictors were trained with the cell line data and then evaluated with a historical patient cohort. For the UVA-55 cohort, the carboplatin, taxol, and combination predictors significantly stratified responder patients and non-responder patients (p = 0.019, 0.04, 0.014) with sensitivity = 91%, 96%, 93 and NPV = 57%, 67%, 67% in pathologic clinical response. The combination predictor also demons...Continue Reading

References

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Citations

Oct 4, 2012·Future Oncology·Klaus H BaumannAndreas du Bois
Mar 13, 2014·Nature Reviews. Urology·Homayoun ZargarPeter Black
Apr 4, 2013·Database : the Journal of Biological Databases and Curation·Benjamin Frederick GanzfriedLevi Waldron
Dec 20, 2012·Expert Review of Molecular Diagnostics·Maja H Oktay, Pei Hui
Feb 20, 2016·BMC Bioinformatics·Jared S FowlesDaniel L Gustafson
Dec 23, 2015·Assay and Drug Development Technologies·Daniel L GustafsonDan Theodorescu
Aug 27, 2014·PloS One·Leslie M CopeChristopher B Umbricht
Apr 18, 2015·BMC Cancer·Katherine L LloydRichard S Savage
May 18, 2016·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Xianglan ZhangKi-Yeol Kim
Oct 19, 2017·The EMBO Journal·Marlies CortésAntonio Postigo
Oct 21, 2016·Molecular Cancer·Jesus Gonzalez BosquetBrian J Smith
Aug 31, 2017·Scientific Reports·Abel MatondoSung Soo Kim
Dec 6, 2018·BioMed Research International·Hoiseon JeongJu-Han Lee
May 5, 2017·Expert Review of Molecular Diagnostics·Wei-Lei YangRobert C Bast
Nov 21, 2019·International Journal of Oncology·Qun LiuJian Liu
May 24, 2020·Cancer Biomarkers : Section a of Disease Markers·Xue PanSong Gao
Jun 15, 2019·International Journal of Molecular Sciences·Otília MenyhártBalázs Győrffy
Jul 1, 2017·Targeted Oncology·Justin D Lathia, Huiping Liu
Jun 20, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aline TalhoukMichael S Anglesio

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Methods Mentioned

BETA
biopsy

Software Mentioned

COXEN
RMA Bioconductor

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