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

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

Keywords

  • Biomarkers
  • Lung cancer
  • Splicing

ASJC Scopus subject areas

  • Oncology

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    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, D. C., 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, 5(22), 11054-11063.