Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer

Kira Philipsen Prahm; Claus Høgdall; Mona Aarenstrup Karlsen; Ib Jarle Christensen; Guy Wayne Novotny; Steen Knudsen; Anker Hansen; Peter Buhl Jensen; Thomas Jensen; Mansoor Raza Mirza; Anne Weng Ekmann-Gade; Lotte Nedergaard; Estrid Høgdall

doi:10.1371/journal.pone.0174300

Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer

Kira Philipsen Prahm^*, Claus Høgdall, Mona Aarenstrup Karlsen, Ib Jarle Christensen, Guy Wayne Novotny, Steen Knudsen, Anker Hansen, Peter Buhl Jensen, Thomas Jensen, Mansoor Raza Mirza, Anne Weng Ekmann-Gade, Lotte Nedergaard, Estrid Høgdall

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

6 Citationer (Scopus)

44 Downloads (Pure)

Abstract

Objective Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. Methods Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment. Results In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36-1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05-0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: Hazard ratio: 0.69, 95% CI: 0.40-1.19, P = 0.183, OS: Hazard ratio: 0.76, 95% CI: 0.42-1.40, P = 0.386). Conclusion In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.

Originalsprog	Engelsk
Artikelnummer	e0174300
Tidsskrift	PLOS ONE
Vol/bind	12
Udgave nummer	3
Antal sider	15
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0174300
Status	Udgivet - 23 mar. 2017

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1371/journal.pone.0174300Licens: CC BY

Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancerForlagets udgivne version, 923 KBLicens: CC BY

Citationsformater

Prahm, K. P., Høgdall, C., Karlsen, M. A., Christensen, I. J., Novotny, G. W., Knudsen, S., Hansen, A., Jensen, P. B., Jensen, T., Mirza, M. R., Ekmann-Gade, A. W., Nedergaard, L., & Høgdall, E. (2017). Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer. PLOS ONE, 12(3), [e0174300]. https://doi.org/10.1371/journal.pone.0174300

Prahm, KP, Høgdall, C, Karlsen, MA, Christensen, IJ, Novotny, GW, Knudsen, S, Hansen, A, Jensen, PB, Jensen, T, Mirza, MR, Ekmann-Gade, AW, Nedergaard, L & Høgdall, E 2017, 'Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer', PLOS ONE, bind 12, nr. 3, e0174300. https://doi.org/10.1371/journal.pone.0174300

@article{907345e96d984b579fc84f7c2ba30023,

title = "Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer",

abstract = "Objective Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. Methods Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment. Results In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36-1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05-0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: Hazard ratio: 0.69, 95% CI: 0.40-1.19, P = 0.183, OS: Hazard ratio: 0.76, 95% CI: 0.42-1.40, P = 0.386). Conclusion In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.",

author = "Prahm, {Kira Philipsen} and Claus H{\o}gdall and Karlsen, {Mona Aarenstrup} and Christensen, {Ib Jarle} and Novotny, {Guy Wayne} and Steen Knudsen and Anker Hansen and Jensen, {Peter Buhl} and Thomas Jensen and Mirza, {Mansoor Raza} and Ekmann-Gade, {Anne Weng} and Lotte Nedergaard and Estrid H{\o}gdall",

year = "2017",

month = mar,

day = "23",

doi = "10.1371/journal.pone.0174300",

language = "English",

volume = "12",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "3",

}

TY - JOUR

T1 - Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer

AU - Prahm, Kira Philipsen

AU - Høgdall, Claus

AU - Karlsen, Mona Aarenstrup

AU - Christensen, Ib Jarle

AU - Novotny, Guy Wayne

AU - Knudsen, Steen

AU - Hansen, Anker

AU - Jensen, Peter Buhl

AU - Jensen, Thomas

AU - Mirza, Mansoor Raza

AU - Ekmann-Gade, Anne Weng

AU - Nedergaard, Lotte

AU - Høgdall, Estrid

PY - 2017/3/23

Y1 - 2017/3/23

N2 - Objective Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. Methods Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment. Results In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36-1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05-0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: Hazard ratio: 0.69, 95% CI: 0.40-1.19, P = 0.183, OS: Hazard ratio: 0.76, 95% CI: 0.42-1.40, P = 0.386). Conclusion In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.

AB - Objective Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. Methods Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment. Results In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36-1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05-0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: Hazard ratio: 0.69, 95% CI: 0.40-1.19, P = 0.183, OS: Hazard ratio: 0.76, 95% CI: 0.42-1.40, P = 0.386). Conclusion In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.

U2 - 10.1371/journal.pone.0174300

DO - 10.1371/journal.pone.0174300

M3 - Journal article

C2 - 28334047

AN - SCOPUS:85016160210

SN - 1932-6203

VL - 12

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 3

M1 - e0174300

ER -

Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater