Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer

Abstract

The development of reliable gene expression profiling technology is having an increasing impact on our understanding of lung cancer biology. Our study aimed to determine any correlation between the phenotypic heterogeneity and genetic diversity of lung cancer. Microarray analysis was performed on a set of 46 tumor samples and 45 paired nontumor samples of nonsmall cell lung cancer (NSCLC) samples to establish gene signatures in primary adenocarcinomas and squamous-cell carcinomas, determine differentially expressed gene sequences at different stages of the disease and identify sequences with biological significance for tumor progression. After the microarray analysis, the expression level of 92 selected genes was validated by qPCR and the robust Bonferroni test in an independent set of 70 samples composed of 48 tumor samples and 22 nontumor samples. Gene sequences were differentially expressed as a function of tumor type, stage and differentiation grade. High upregulation was observed for KRT15 and PKP1, which may be good markers to distinguish squamous-cell carcinoma samples. High downregulation was observed for DSG3 in stage IA adenocarcinomas.Lung cancer is the leading cause of cancer death in the United States 1 and worldwide. The two major forms of lung cancer are nonsmall cell lung cancer (NSCLC %85% of all lung cancers) and small-cell lung cancer (SCLC %15%). NSCLC can be divided into three major histological subtypes: squamous-cell carcinoma, adenocarcinoma and large-cell lung cancer. Smoking causes all types of lung cancer but is most strongly linked with SCLC and squamous-cell carcinoma, while adenocarcinoma is the most frequent type in patients who have never smoked.2-5 Patients with early-stage NSCLC who undergo curative resection still have a substantial risk of developing metastases. The 5-year survival rates for patients with Stage IA and IB NSCLC are only 67 and 57%, respectively.

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

“…, 26 GSE18842, 27 and GSE31210 28 ) from GEO. This analysis showed that 96 pseudogenes were misregulated in GSE19188, whereas 40 were in GSE30219, 76 in GSE18842, and 54 in GSE31210 (Figure 1A; Table S2).…”

MicroRNA 4423 is a primate-specific regulator of airway epithelial cell differentiation and lung carcinogenesis

“…With regards to lung cancer, using a previously published gene expression study from our group (17), we found that genes that decrease upon miR-4423 overexpression are enriched among genes whose expression is increased in airway epithelium from patients with lung cancer (FDR q < 0.001; GSEA). We also found in three datasets (36)(37)(38) that the genes altered upon miR-4423 overexpression were significantly enriched among genes whose expression changed in the opposite direction in lung ADC and SCC relative to adjacent normal tissue (FDR q < 0.05; GSEA; SI Appendix, Fig. S21 A and B).…”

Transforming growth factor-beta signaling network regulates plasticity and lineage commitment of lung cancer cells

“…All of these TBR2-negative tumors were morphologically pure SCCs and expressed high levels of KRT15 and the transcription factors SKI, p63 and SOX2 (Figures 3a and b), which are known prognostic indicators and markers of SCC. [26][27][28] In contrast, the TBR2-positive tumors were either ADCs or SCs, which had low or no expression of SKI, p63, SOX2 or KRT15 (Figure 3b). To determine whether the loss of TBR2 expression indicated that the TGF-beta signaling had a mechanistic role in the development of ADC and SCC, we used three different approaches: (1) genetic or pharmacological inactivation of TGF-beta signaling in premalignant and cancer-derived cell lines; (2) dominant interference with the formation of SMAD complexes in these cell lines; and (3) constitutive activation of the TGF-beta receptor signaling in premalignant KrasG12D p53 KO cells and tumors.…”