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
U2 - 10.18632/oncotarget.2609
DO - 10.18632/oncotarget.2609
M3 - Article
C2 - 25373410
AN - SCOPUS:84917738647
SN - 1949-2553
VL - 5
SP - 11054
EP - 11063
JO - Oncotarget
JF - Oncotarget
IS - 22
ER -