期刊
JOURNAL OF THORACIC ONCOLOGY
卷 12, 期 1, 页码 65-76出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2016.08.141
关键词
Lung squamous cell carcinoma; Prognostic classifier; Biomarker; Microarray; Gene expression
资金
- Intramural Research Program of the National Cancer Institute, National Institutes of Health
- Department of Defense Congressionally Directed Medical Research Program [PR093793]
- Health Research Board [CPFP/2012/2]
- Norwegian Cancer Society
- National Cancer Center Research and Development Fund [26A-1]
- NATIONAL CANCER INSTITUTE [ZIABC011492, Z01BC005480] Funding Source: NIH RePORTER
Introduction: There are no validated molecular methods that prospectively identify patients with surgically resected lung squamous cell carcinoma (SCC) at high risk for recurrence. By focusing on the expression of genes with known functions in development of lung SCC and prognosis, we sought to develop a robust prognostic classifier of early stage lung SCC. Methods: The expression of 253 genes selected by literature search was evaluated in microarrays from 107 stage I/II tumors. Associations with survival were evaluated by Cox regression and Kaplan-Meier survival analyses in two independent cohorts of 121 and 91 patients with SCC, respectively. A classifier score based on multivariable Cox regression was derived and exam fined in six additional publicly available data sets of stage I/II lung SCC expression profiles (n = 358). The prognostic value of this classifier was evaluated in meta analysis of patients with stage I/II (n = 479) and stage I (n = 326) lung SCC. Results: Dual specificity phosphatase 6 gene (DUSP6) and actinin alpha 4 gene (ACTN4) were associated with prognostic outcome in two independent patient cohorts. Their expression values were utilized to develop a classifier that identified patients with stage I/II lung SCC at high risk for recurrence (hazard ratio [HR] = 4.7, p = 0.018) or cancer-specific mortality (HR = 3.5, p = 0.016). This classifier also identified patients at high risk for recurrence (HR = 2.7, p = 0.008) or death (HR = 2.2, p = 0.001) in publicly available data sets of stage I/II and in meta analysis of stage I patients. Conclusions: We have established and validated a prognostic classifier to inform clinical management of patients with lung SCC after surgical resection. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.
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