Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in nonsmoking women.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
A novel biomarker for NSCLC is identified.
Lu
Tzu-Pin
TP
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Tsai
Mong-Hsun
MH
Lee
Jang-Ming
JM
Hsu
Chung-Ping
CP
Chen
Pei-Chun
PC
Lin
Chung-Wu
CW
Shih
Jin-Yuan
JY
Yang
Pan-Chyr
PC
Hsiao
Chuhsing Kate
CK
Lai
Liang-Chuan
LC
Chuang
Eric Y
EY
D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins; D015398:Signal Transduction; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C491228:SEMA5A protein, human; D039961:Semaphorins