MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer

John K. Chan, Tuyen K. Kiet, Kevin Blansit, Rashmi Ramasubbaiah, Joan F. Hilton, Daniel S. Kapp, Daniela Matei

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Abstract

Objective To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer. Methods Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards. Results MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2 months; p = 0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR = 2.04, 95% CI: 1.12-3.72; p = 0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2 months, p = 0.04 for high vs. low ALCAM; 7.9 vs. 2.3 months, p < 0.01 for low vs. high EHD1). Conclusions Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response to anti-angiogenic therapy.

Original languageEnglish (US)
Pages (from-to)568-574
Number of pages7
JournalGynecologic Oncology
Volume133
Issue number3
DOIs
StatePublished - Jun 2014

Fingerprint

Ovarian Neoplasms
Activated-Leukocyte Cell Adhesion Molecule
Biomarkers
Disease-Free Survival
Atlases
Epithelial Cells
Neoplasms
Therapeutics
Genome
Tumor Cell Line
Transfection
Cell Cycle
Multivariate Analysis
Apoptosis
Gene Expression
Polymerase Chain Reaction
Genes

Keywords

  • Anti-angiogenic therapy
  • MiR-378
  • MicroRNA
  • Ovarian cancer
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Chan, J. K., Kiet, T. K., Blansit, K., Ramasubbaiah, R., Hilton, J. F., Kapp, D. S., & Matei, D. (2014). MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. Gynecologic Oncology, 133(3), 568-574. https://doi.org/10.1016/j.ygyno.2014.03.564

MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. / Chan, John K.; Kiet, Tuyen K.; Blansit, Kevin; Ramasubbaiah, Rashmi; Hilton, Joan F.; Kapp, Daniel S.; Matei, Daniela.

In: Gynecologic Oncology, Vol. 133, No. 3, 06.2014, p. 568-574.

Research output: Contribution to journalArticle

Chan, JK, Kiet, TK, Blansit, K, Ramasubbaiah, R, Hilton, JF, Kapp, DS & Matei, D 2014, 'MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer', Gynecologic Oncology, vol. 133, no. 3, pp. 568-574. https://doi.org/10.1016/j.ygyno.2014.03.564
Chan JK, Kiet TK, Blansit K, Ramasubbaiah R, Hilton JF, Kapp DS et al. MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. Gynecologic Oncology. 2014 Jun;133(3):568-574. https://doi.org/10.1016/j.ygyno.2014.03.564
Chan, John K. ; Kiet, Tuyen K. ; Blansit, Kevin ; Ramasubbaiah, Rashmi ; Hilton, Joan F. ; Kapp, Daniel S. ; Matei, Daniela. / MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. In: Gynecologic Oncology. 2014 ; Vol. 133, No. 3. pp. 568-574.
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abstract = "Objective To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer. Methods Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards. Results MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2 months; p = 0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR = 2.04, 95{\%} CI: 1.12-3.72; p = 0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2 months, p = 0.04 for high vs. low ALCAM; 7.9 vs. 2.3 months, p < 0.01 for low vs. high EHD1). Conclusions Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response to anti-angiogenic therapy.",
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AU - Chan, John K.

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AU - Blansit, Kevin

AU - Ramasubbaiah, Rashmi

AU - Hilton, Joan F.

AU - Kapp, Daniel S.

AU - Matei, Daniela

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N2 - Objective To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer. Methods Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards. Results MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2 months; p = 0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR = 2.04, 95% CI: 1.12-3.72; p = 0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2 months, p = 0.04 for high vs. low ALCAM; 7.9 vs. 2.3 months, p < 0.01 for low vs. high EHD1). Conclusions Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response to anti-angiogenic therapy.

AB - Objective To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer. Methods Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards. Results MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2 months; p = 0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR = 2.04, 95% CI: 1.12-3.72; p = 0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2 months, p = 0.04 for high vs. low ALCAM; 7.9 vs. 2.3 months, p < 0.01 for low vs. high EHD1). Conclusions Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response to anti-angiogenic therapy.

KW - Anti-angiogenic therapy

KW - MiR-378

KW - MicroRNA

KW - Ovarian cancer

KW - Survival

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