Dataset Information

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-small-cell 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 hMENA?v6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENA?v6. Enforced expression of hMENA?v6 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 pan-hMENA/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.

SUBMITTER: Bria E

PROVIDER: S-EPMC4294370 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Bria Emilio E Di Modugno Francesca F Sperduti Isabella I Iapicca Pierluigi P Visca Paolo P Alessandrini Gabriele G Antoniani Barbara B Pilotto Sara S Ludovini Vienna V Vannucci Jacopo J Bellezza Guido G Sidoni Angelo A Tortora Giampaolo G Radisky Derek C DC Crinò Lucio L Cognetti Francesco F Facciolo Francesco F Mottolese Marcella M Milella Michele M Nisticò Paola P

Oncotarget 20141101 22

Risk assessment and treatment choice remain a challenge in early non-small-cell 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 ...[more]

PMID: 25373410

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Project description:Background Lymph node involvement is one of the important prognostic factors for early-stage lung cancer. However, in lymph node-negative (N0) lung cancer the recurrent rate may be as high as 30%. We aimed to study potential prognostic factors including clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status in this lung cancer population. Methods We retrospectively reviewed the medical records and pathological examinations of patients with completely resected N0 pulmonary adenocarcinoma treated in our institute between 2009 and 2016. We used Cobas® test to determine EGFR mutation status. Recurrence-free survival (RFS) was analyzed by univariable and multivariable Cox regression analyses. Results We recruited 220 patients with median duration of follow up 5 years. Majority of these patients were in stage I (80%) and did not receive adjuvant therapy (86%). There were 53% with EGFR mutations which comprised of exon 19 deletion 51% and L858R 43%. Recurrence occurred in 64 out of 220 patients (29%). The median time to recurrence was 2.1 years. Statistically significant prognostic factors in both univariate and multivariate analyses included tumor size ≥4 centimeter (cm) (HR: 1.94; 95% CI: 1.03–3.67), visceral pleural invasion (HR: 2.53; 95% CI: 1.34–4.79), tumor necrosis (HR: 2.45; 95% CI: 1.13–5.31) and bronchial resection margin <2 cm (HR: 1.96; 95% CI: 1.10–3.51). However, presence of sensitizing EGFR mutation was not found to be a significant prognostic factor (HR: 1.20; 95% CI: 0.66–2.18; P=0.56). Conclusions In N0 surgically resected lung adenocarcinoma, there were significant pathological prognostic factors including tumor 4 cm or more, visceral pleural invasion, tumor necrosis and bronchial resection margin less than 2 cm. Mutation of EGFR is not a significant prognostic factor to determine the risk of recurrence in this population and their risks shall be determined by the other poor prognostic factors.

Dataset Information

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

Publications

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

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