Abstract
Although cigarette smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. The genetic mechanisms of carcinogenesis in nonsmokers are unclear, but semaphorins have been suggested to play a role as lung tumor suppressors. This report is a comprehensive analysis of the molecular signature of nonsmoking female lung cancer patients in Taiwan, with a particular focus on the semaphorin gene family. Sixty pairs of tumor and adjacent normal lung tissue specimens were analyzed by using Affymetrix U133plus2.0 expression arrays. Differentially expressed genes in tumor tissues were identified by a paired t test and validated by reverse transcriptase-PCR and immunohistochemistry. Functional analysis was conducted by using Ingenuity Pathway Analysis as well as gene set enrichment analysis and sigPathway algorithms. Kaplan-Meier survival analyses were used to evaluate the association of SEMA5A expression and clinical outcome. We identified 687 differentially expressed genes in non-small cell lung carcinoma (NSCLC). Many of these genes, most notably the semaphorin family, were participants in the axon guidance signaling pathway. The downregulation of SEMA5A in tumor tissue, both at the transcriptional and translational levels, was associated with poor survival among nonsmoking women with NSCLC. In summary, several semaphorin gene family members were identified as potential therapeutic targets, and SEMA5A may be useful as a prognostic biomarker for NSCLC, which may also be gender specific in Taiwanese patients. A novel biomarker for NSCLC is identified.
Highlights
IntroductionLung cancer is the leading cause of cancer-related death worldwide and brings significant socioeconomic impact to patients, their families, and society as a whole
Lung cancer is the leading cause of cancer-related death worldwide and brings significant socioeconomic impact to patients, their families, and society as a whole.Authors' Affiliations: 1Graduate Institute of Biomedical Electronics and Bioinformatics, 2Graduate Institute of Physiology, 3Institute of Biotechnology, 4Department of Public Health, and 5Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University; Departments of 6Surgery, 7Internal Medicine, and 8Pathology; 9National Clinical Trial and Research Center, National Taiwan University Hospital, Taipei, Taiwan; and 10Division of Thoracic Surgery, Taichung Veterans General Hospital, Taichung, TaiwanNote: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online.T-P
Clinical characteristics of patients In this study, we collected 120 pairs of cancer and adjacent normal lung tissue specimens from nonsmoking female lung cancer patients who were admitted to National Taiwan University Hospital or Taichung Veterans General Hospital
Summary
Lung cancer is the leading cause of cancer-related death worldwide and brings significant socioeconomic impact to patients, their families, and society as a whole. Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). Cigarette smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. The genetic mechanisms of carcinogenesis in nonsmokers are unclear, but semaphorins have been suggested to play a role as lung tumor suppressors. This report is a comprehensive analysis of the molecular signature of nonsmoking female lung cancer patients in Taiwan, with a particular focus on the semaphorin gene family
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