Identification of high-grade serous ovarian cancer miRNA species associated with survival and drug response in patients receiving neoadjuvant chemotherapy: A retrospective longitudinal analysis using matched tumor biopsies

M. Petrillo, G. F. Zannoni, L. Beltrame, E. Martinelli, A. DiFeo, L. Paracchini, I. Craparotta, L. Mannarino, G. Vizzielli, G. Scambia, M. D'Incalci, C. Romualdi, S. Marchini

Research output: Contribution to journalArticle

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Abstract

Background: Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum (Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen. Patients and methods: One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC-IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis. Results: Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression- free survival (P0.05). Kaplan-Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P>0.001). Conclusions: This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.

Original languageEnglish
Article numbermdw007
Pages (from-to)625-634
Number of pages10
JournalAnnals of Oncology
Volume27
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

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MicroRNAs
Ovarian Neoplasms
Biopsy
Drug Therapy
Survival
Platinum
Pharmaceutical Preparations
Neoplasms
Disease-Free Survival
Real-Time Polymerase Chain Reaction
Multivariate Analysis
Biomarkers
Phosphorylation
Genome
Staining and Labeling
Therapeutics
Ovarian epithelial cancer

Keywords

  • High-grade serous ovarian cancer
  • Longitudinal matched tumor biopsies analysis, miR-181a-5p
  • Neoadjuvant chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Identification of high-grade serous ovarian cancer miRNA species associated with survival and drug response in patients receiving neoadjuvant chemotherapy : A retrospective longitudinal analysis using matched tumor biopsies. / Petrillo, M.; Zannoni, G. F.; Beltrame, L.; Martinelli, E.; DiFeo, A.; Paracchini, L.; Craparotta, I.; Mannarino, L.; Vizzielli, G.; Scambia, G.; D'Incalci, M.; Romualdi, C.; Marchini, S.

In: Annals of Oncology, Vol. 27, No. 4, mdw007, 01.04.2016, p. 625-634.

Research output: Contribution to journalArticle

Petrillo, M. ; Zannoni, G. F. ; Beltrame, L. ; Martinelli, E. ; DiFeo, A. ; Paracchini, L. ; Craparotta, I. ; Mannarino, L. ; Vizzielli, G. ; Scambia, G. ; D'Incalci, M. ; Romualdi, C. ; Marchini, S. / Identification of high-grade serous ovarian cancer miRNA species associated with survival and drug response in patients receiving neoadjuvant chemotherapy : A retrospective longitudinal analysis using matched tumor biopsies. In: Annals of Oncology. 2016 ; Vol. 27, No. 4. pp. 625-634.
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abstract = "Background: Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum (Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen. Patients and methods: One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC-IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis. Results: Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression- free survival (P0.05). Kaplan-Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P>0.001). Conclusions: This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.",
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T1 - Identification of high-grade serous ovarian cancer miRNA species associated with survival and drug response in patients receiving neoadjuvant chemotherapy

T2 - A retrospective longitudinal analysis using matched tumor biopsies

AU - Petrillo, M.

AU - Zannoni, G. F.

AU - Beltrame, L.

AU - Martinelli, E.

AU - DiFeo, A.

AU - Paracchini, L.

AU - Craparotta, I.

AU - Mannarino, L.

AU - Vizzielli, G.

AU - Scambia, G.

AU - D'Incalci, M.

AU - Romualdi, C.

AU - Marchini, S.

PY - 2016/4/1

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N2 - Background: Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum (Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen. Patients and methods: One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC-IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis. Results: Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression- free survival (P0.05). Kaplan-Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P>0.001). Conclusions: This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.

AB - Background: Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum (Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen. Patients and methods: One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC-IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis. Results: Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression- free survival (P0.05). Kaplan-Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P>0.001). Conclusions: This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.

KW - High-grade serous ovarian cancer

KW - Longitudinal matched tumor biopsies analysis, miR-181a-5p

KW - Neoadjuvant chemotherapy

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