Identification of a Novel Biomarker, SEMA5A, for Non–Small Cell Lung Carcinoma in Nonsmoking Women

Abstract

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.Impact: A novel biomarker for NSCLC is identified. Cancer Epidemiol Biomarkers Prev; 19(10); 2590-7. ©2010 AACR.

Semaphorin 5A and plexin-B3 regulate human glioma cell motility and morphology through Rac1 and the actin cytoskeleton

“…In fact, silencing Sema5A expression in U87-MG cells, or low level of endogenous Sema5A in rat C6 cells (vs U87-MG) correlate with enhanced invasiveness in glioma cells. In line with this, a recent report has also demonstrated a significant downregulation of the Sema5A transcript and protein in nonsmall cell lung carcinoma, which correlates with poor survival of patients (Lu et al, 2010). Consistent with our working hypothesis but from a different perspective, a recent study has reported a novel plexin-B3 missense mutation in human pancreatic ductal adenocarcinomas that prevents its interaction with Sema5A, hence impairing their signaling and contributing to tumor progression (Balakrishnan et al, 2009).…”

“…Drosophila Sema5c, for instance, is required for tumorigenicity induced by deletion of the tumor-suppressor gene l(2)gl (Woodhouse et al, 2003). Although semaphorin 5A (Sema5A) was shown to be associated with the aggressive nature of pancreatic, prostate and gastric cancers by two laboratories (Sadanandam et al, 2007(Sadanandam et al, , 2010Pan et al, 2010), a recent report has demonstrated a downregulation of Sema5A expression in non-small cell lung carcinoma, which is associated with poor survival of patients (Lu et al, 2010). The Sema5A transcript has formerly been detected in primary astrocytomas (Rickman et al, 2001).…”

Long Noncoding RNA PVT1 Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

“…Four independent data sets from GSE18842 (22), GSE19188 (23), GSE19804 (24), and GSE30219 (25) were included in this study. The raw CEL files were downloaded from GEO database and normalized using Robust Multichip Average (RMA).…”

ADAM9 Promotes Lung Cancer Metastases to Brain by a Plasminogen Activator-Based Pathway

“…After retrieving the raw data, a quantile normalization method was performed for each dataset to remove the potential systematic biases. Survival analyses were performed based on the procedures in our previous studies (20,21). Briefly, for each gene, samples were divided into two groups according to the following criteria: (i) a high group, in which gene expression levels of the specific gene were higher than the median in all samples; and (ii) a low group, in which gene expression levels of the specific gene were lower than the median in all samples.…”