Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

Emilio Bria, Francesca Di Modugno, Isabella Sperduti, Pierluigi Iapicca, Paolo Visca, Gabriele Alessandrini, Barbara Antoniani, Sara Pilotto, Vienna Ludovini, Jacopo Vannucci, Guido Bellezza, Angelo Sidoni, Giampaolo Tortora, Derek C. Radisky, Lucio Crinò, Francesco Cognetti, Francesco Facciolo, Marcella Mottolese, Michele Milella, Paola Nisticò

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Risk assessment and treatment choice remain a challenge in early non-smallcell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low panhMENA/ high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk.

Original languageEnglish
Pages (from-to)11054-11063
Number of pages10
JournalOncotarget
Volume5
Issue number22
Publication statusPublished - 2014

Fingerprint

Alternative Splicing
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Protein Isoforms
Survival
Actin Cytoskeleton
Neoplasms
Multivariate Analysis
Lymph Nodes
Recurrence
Therapeutics

Keywords

  • Biomarkers
  • Lung cancer
  • Splicing

ASJC Scopus subject areas

  • Oncology

Cite this

Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer. / Bria, Emilio; Di Modugno, Francesca; Sperduti, Isabella; Iapicca, Pierluigi; Visca, Paolo; Alessandrini, Gabriele; Antoniani, Barbara; Pilotto, Sara; Ludovini, Vienna; Vannucci, Jacopo; Bellezza, Guido; Sidoni, Angelo; Tortora, Giampaolo; Radisky, Derek C.; Crinò, Lucio; Cognetti, Francesco; Facciolo, Francesco; Mottolese, Marcella; Milella, Michele; Nisticò, Paola.

In: Oncotarget, Vol. 5, No. 22, 2014, p. 11054-11063.

Research output: Contribution to journalArticle

Bria, E, Di Modugno, F, Sperduti, I, Iapicca, P, Visca, P, Alessandrini, G, Antoniani, B, Pilotto, S, Ludovini, V, Vannucci, J, Bellezza, G, Sidoni, A, Tortora, G, Radisky, DC, Crinò, L, Cognetti, F, Facciolo, F, Mottolese, M, Milella, M & Nisticò, P 2014, 'Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer', Oncotarget, vol. 5, no. 22, pp. 11054-11063.
Bria E, Di Modugno F, Sperduti I, Iapicca P, Visca P, Alessandrini G et al. Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer. Oncotarget. 2014;5(22):11054-11063.
Bria, Emilio ; Di Modugno, Francesca ; Sperduti, Isabella ; Iapicca, Pierluigi ; Visca, Paolo ; Alessandrini, Gabriele ; Antoniani, Barbara ; Pilotto, Sara ; Ludovini, Vienna ; Vannucci, Jacopo ; Bellezza, Guido ; Sidoni, Angelo ; Tortora, Giampaolo ; Radisky, Derek C. ; Crinò, Lucio ; Cognetti, Francesco ; Facciolo, Francesco ; Mottolese, Marcella ; Milella, Michele ; Nisticò, Paola. / Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer. In: Oncotarget. 2014 ; Vol. 5, No. 22. pp. 11054-11063.
@article{afe10dd4f84e41c59c0aa5d6f1adf470,
title = "Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer",
abstract = "Risk assessment and treatment choice remain a challenge in early non-smallcell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low panhMENA/ high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk.",
keywords = "Biomarkers, Lung cancer, Splicing",
author = "Emilio Bria and {Di Modugno}, Francesca and Isabella Sperduti and Pierluigi Iapicca and Paolo Visca and Gabriele Alessandrini and Barbara Antoniani and Sara Pilotto and Vienna Ludovini and Jacopo Vannucci and Guido Bellezza and Angelo Sidoni and Giampaolo Tortora and Radisky, {Derek C.} and Lucio Crin{\`o} and Francesco Cognetti and Francesco Facciolo and Marcella Mottolese and Michele Milella and Paola Nistic{\`o}",
year = "2014",
language = "English",
volume = "5",
pages = "11054--11063",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "22",

}

TY - JOUR

T1 - Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

AU - Bria, Emilio

AU - Di Modugno, Francesca

AU - Sperduti, Isabella

AU - Iapicca, Pierluigi

AU - Visca, Paolo

AU - Alessandrini, Gabriele

AU - Antoniani, Barbara

AU - Pilotto, Sara

AU - Ludovini, Vienna

AU - Vannucci, Jacopo

AU - Bellezza, Guido

AU - Sidoni, Angelo

AU - Tortora, Giampaolo

AU - Radisky, Derek C.

AU - Crinò, Lucio

AU - Cognetti, Francesco

AU - Facciolo, Francesco

AU - Mottolese, Marcella

AU - Milella, Michele

AU - Nisticò, Paola

PY - 2014

Y1 - 2014

N2 - Risk assessment and treatment choice remain a challenge in early non-smallcell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low panhMENA/ high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk.

AB - Risk assessment and treatment choice remain a challenge in early non-smallcell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low panhMENA/ high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk.

KW - Biomarkers

KW - Lung cancer

KW - Splicing

UR - http://www.scopus.com/inward/record.url?scp=84917738647&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84917738647&partnerID=8YFLogxK

M3 - Article

C2 - 25373410

AN - SCOPUS:84917738647

VL - 5

SP - 11054

EP - 11063

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 22

ER -