Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression

M. T. Marino, A. Grilli, C. Baricordi, M. C. Manara, S. Ventura, R. S. Pinca, M. Bellenghi, M. Calvaruso, G. Mattia, D. Donati, C. Tripodo, P. Picci, S. Ferrari, K. Scotlandi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

BACKGROUND: At diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients.

PATIENTS AND METHODS: Specimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied. Sixty-eight patients (62%) remained disease-free and 41 (38%) relapsed (median follow-up: 67 months, range 9-241 months). Expression of miR-34a and of some of its targets (cyclin D1, bcl-2, SIRT1 and YY1) was evaluated by qRT-PCR using TaqMan MicroRNA Assays and/or by immunohistochemistry on tissue microarrays from the same patients.

RESULTS: High expression of miR-34a in localized tumors was significantly related to better event-free and overall survival (P = 0.004). Relevance of miR-34a was confirmed by using different calibrators (normal mesenchymal stem cells and different normal tissues). By multivariate Cox regression analysis, low miR-34a expression as well as nontotal necrosis and high levels of lactate dehydrogenase were all confirmed as independent risk factors associated with poor outcome. Expression of miR-34a was lower in metastases than in primary tumors. It inversely correlated with expression of cyclin D1 and Ki-67.

CONCLUSIONS: By demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment.

Original languageEnglish
Pages (from-to)2080-2086
Number of pages7
JournalAnnals of Oncology
Volume25
Issue number10
DOIs
Publication statusPublished - Oct 1 2014

Fingerprint

Ewing's Sarcoma
Cyclin D1
Neoplasm Metastasis
MicroRNAs
Mesenchymal Stromal Cells
L-Lactate Dehydrogenase
Disease-Free Survival
Neoplasms
Necrosis
Immunohistochemistry
Regression Analysis
Drug Therapy
Polymerase Chain Reaction

Keywords

  • cyclin D1
  • Ewing sarcoma
  • Ki-67
  • miR-34a
  • prognostic biomarkers

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression. / Marino, M. T.; Grilli, A.; Baricordi, C.; Manara, M. C.; Ventura, S.; Pinca, R. S.; Bellenghi, M.; Calvaruso, M.; Mattia, G.; Donati, D.; Tripodo, C.; Picci, P.; Ferrari, S.; Scotlandi, K.

In: Annals of Oncology, Vol. 25, No. 10, 01.10.2014, p. 2080-2086.

Research output: Contribution to journalArticle

Marino, MT, Grilli, A, Baricordi, C, Manara, MC, Ventura, S, Pinca, RS, Bellenghi, M, Calvaruso, M, Mattia, G, Donati, D, Tripodo, C, Picci, P, Ferrari, S & Scotlandi, K 2014, 'Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression', Annals of Oncology, vol. 25, no. 10, pp. 2080-2086. https://doi.org/10.1093/annonc/mdu249
Marino, M. T. ; Grilli, A. ; Baricordi, C. ; Manara, M. C. ; Ventura, S. ; Pinca, R. S. ; Bellenghi, M. ; Calvaruso, M. ; Mattia, G. ; Donati, D. ; Tripodo, C. ; Picci, P. ; Ferrari, S. ; Scotlandi, K. / Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression. In: Annals of Oncology. 2014 ; Vol. 25, No. 10. pp. 2080-2086.
@article{6b78b32cab764f41a1c00f3c7f901906,
title = "Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression",
abstract = "BACKGROUND: At diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients.PATIENTS AND METHODS: Specimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied. Sixty-eight patients (62{\%}) remained disease-free and 41 (38{\%}) relapsed (median follow-up: 67 months, range 9-241 months). Expression of miR-34a and of some of its targets (cyclin D1, bcl-2, SIRT1 and YY1) was evaluated by qRT-PCR using TaqMan MicroRNA Assays and/or by immunohistochemistry on tissue microarrays from the same patients.RESULTS: High expression of miR-34a in localized tumors was significantly related to better event-free and overall survival (P = 0.004). Relevance of miR-34a was confirmed by using different calibrators (normal mesenchymal stem cells and different normal tissues). By multivariate Cox regression analysis, low miR-34a expression as well as nontotal necrosis and high levels of lactate dehydrogenase were all confirmed as independent risk factors associated with poor outcome. Expression of miR-34a was lower in metastases than in primary tumors. It inversely correlated with expression of cyclin D1 and Ki-67.CONCLUSIONS: By demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment.",
keywords = "cyclin D1, Ewing sarcoma, Ki-67, miR-34a, prognostic biomarkers",
author = "Marino, {M. T.} and A. Grilli and C. Baricordi and Manara, {M. C.} and S. Ventura and Pinca, {R. S.} and M. Bellenghi and M. Calvaruso and G. Mattia and D. Donati and C. Tripodo and P. Picci and S. Ferrari and K. Scotlandi",
year = "2014",
month = "10",
day = "1",
doi = "10.1093/annonc/mdu249",
language = "English",
volume = "25",
pages = "2080--2086",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "10",

}

TY - JOUR

T1 - Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression

AU - Marino, M. T.

AU - Grilli, A.

AU - Baricordi, C.

AU - Manara, M. C.

AU - Ventura, S.

AU - Pinca, R. S.

AU - Bellenghi, M.

AU - Calvaruso, M.

AU - Mattia, G.

AU - Donati, D.

AU - Tripodo, C.

AU - Picci, P.

AU - Ferrari, S.

AU - Scotlandi, K.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - BACKGROUND: At diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients.PATIENTS AND METHODS: Specimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied. Sixty-eight patients (62%) remained disease-free and 41 (38%) relapsed (median follow-up: 67 months, range 9-241 months). Expression of miR-34a and of some of its targets (cyclin D1, bcl-2, SIRT1 and YY1) was evaluated by qRT-PCR using TaqMan MicroRNA Assays and/or by immunohistochemistry on tissue microarrays from the same patients.RESULTS: High expression of miR-34a in localized tumors was significantly related to better event-free and overall survival (P = 0.004). Relevance of miR-34a was confirmed by using different calibrators (normal mesenchymal stem cells and different normal tissues). By multivariate Cox regression analysis, low miR-34a expression as well as nontotal necrosis and high levels of lactate dehydrogenase were all confirmed as independent risk factors associated with poor outcome. Expression of miR-34a was lower in metastases than in primary tumors. It inversely correlated with expression of cyclin D1 and Ki-67.CONCLUSIONS: By demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment.

AB - BACKGROUND: At diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients.PATIENTS AND METHODS: Specimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied. Sixty-eight patients (62%) remained disease-free and 41 (38%) relapsed (median follow-up: 67 months, range 9-241 months). Expression of miR-34a and of some of its targets (cyclin D1, bcl-2, SIRT1 and YY1) was evaluated by qRT-PCR using TaqMan MicroRNA Assays and/or by immunohistochemistry on tissue microarrays from the same patients.RESULTS: High expression of miR-34a in localized tumors was significantly related to better event-free and overall survival (P = 0.004). Relevance of miR-34a was confirmed by using different calibrators (normal mesenchymal stem cells and different normal tissues). By multivariate Cox regression analysis, low miR-34a expression as well as nontotal necrosis and high levels of lactate dehydrogenase were all confirmed as independent risk factors associated with poor outcome. Expression of miR-34a was lower in metastases than in primary tumors. It inversely correlated with expression of cyclin D1 and Ki-67.CONCLUSIONS: By demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment.

KW - cyclin D1

KW - Ewing sarcoma

KW - Ki-67

KW - miR-34a

KW - prognostic biomarkers

UR - http://www.scopus.com/inward/record.url?scp=84930804356&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930804356&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdu249

DO - 10.1093/annonc/mdu249

M3 - Article

C2 - 25015333

AN - SCOPUS:84930804356

VL - 25

SP - 2080

EP - 2086

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 10

ER -