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Efficacy of adjuvant chemotherapy for non-small cell lung cancer assessed by metastatic potential associated with ACTN4.
- Source :
-
Oncotarget [Oncotarget] 2016 May 31; Vol. 7 (22), pp. 33165-78. - Publication Year :
- 2016
-
Abstract
- Although several clinical trials have demonstrated the benefits of platinum-combined adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), predictive biomarkers for the efficacy of such therapy have not yet been identified. Selection of patients with high metastatic ability in the early stage of non-small cell lung cancer (NSCLC) has the potential to predict clinical benefit of adjuvant chemotherapy (ADJ).In order to develop a predictive biomarker for efficacy of ADJ, we reanalyzed patient data using a public database enrolled by JBR.10, which was a clinical trial to probe the clinical benefits of ADJ in stage-IB/II patients with NSCLC. The patients who were enrolled by JBR.10 were classified into 2 subgroups according to expression of the ACTN4 transcript: ACTN4 positive (ACTN4 (+)) and ACTN4 negative (ACTN4 (-)). In the ACTN4 (+) group, overall survival (OS) was significantly higher in the ADJ subgroup compared with the observation subgroup (OBS), indicating a significant survival benefit of ADJ. However, no difference in OS was found between ADJ and OBS groups in ACTN4 (-). Although ACTN4 expression level did not correlate with the chemosensitivity of cancer cell lines for cytotoxic drugs, the metastatic potential of A549 lung adenocarcinoma cells was significantly reduced by ACTN4 shRNA in in vitro assays and in an animal transplantation model. The clinical and preclinical data suggested that ACTN4 is a potential predictive biomarker for efficacy of ADJ in stage-IB/II patients with NSCLC, by reflecting the metastatic potential of tumor cells.<br />Competing Interests: The authors declare that they have no competing interests.
- Subjects :
- A549 Cells
Adenocarcinoma genetics
Adenocarcinoma metabolism
Adenocarcinoma secondary
Adenocarcinoma of Lung
Aged
Animals
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung mortality
Carcinoma, Non-Small-Cell Lung secondary
Cell Movement drug effects
Chemotherapy, Adjuvant
Clinical Trials as Topic
Databases, Factual
Dose-Response Relationship, Drug
Female
Humans
Kaplan-Meier Estimate
Lung Neoplasms metabolism
Lung Neoplasms mortality
Lung Neoplasms pathology
Male
Mice, SCID
Middle Aged
Neoplasm Invasiveness
Neoplasm Staging
Pneumonectomy
Proportional Hazards Models
RNA Interference
Time Factors
Transfection
Treatment Outcome
Xenograft Model Antitumor Assays
Actinin metabolism
Adenocarcinoma drug therapy
Antineoplastic Agents therapeutic use
Biomarkers, Tumor metabolism
Carcinoma, Non-Small-Cell Lung drug therapy
Lung Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27121206
- Full Text :
- https://doi.org/10.18632/oncotarget.8890