Project description:The functions of EGR1, a multifunctional transcription factor, in prostate cancer are well documented. However, little is known about the functions of EGR1 in lung cancer. we observed the function of EGR1 in non-small cell lung carcinoma (NSCLC) and identified the genes that influence cell fate and tumor development. We used microarrays to detail the global programme of gene expression and identified genes differentially expressed when EGR1-overexpressed.
Project description:The tumor microenvironment strongly influences cancer development, progression and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-beta signaling pathway. We have identified a subset of 11 genes that formed a prognostic gene expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene expression changes revealed prominent involvement of the focal adhesion and MAPK signalling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture micro-dissected corresponding primary tumor stroma compared to the matched normal lung. Six of these 14 genes could be induced by TGF-beta1 in NF. The results establish the prognostic impact of CAF-associated gene expression changes in NSCLC patients. This SuperSeries is composed of the following subset Series: GSE22862: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [expression profiling_CAFs] GSE22863: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [expression profiling_NSCLC stroma] GSE27284: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [methylation profiling] GSE27289: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [genome variation profiling]
Project description:Affymetrix exon array data set (HuEx-1.0_st) derived from matched pairs of non-small cell lung cancer (NSCLC) and normal adjacent lung tissue (NAT). This data set includes both the adenocarcinoma (AdCa) as well as the squamous cell carcinoma (SCC) subtype of NSCLC.
Project description:Non-small cell lung cancer (NSCLC, n=22) and normal adjacent control biopsies (n=18) from patients with lung cancer were obtained for Affymetrix GeneChip analysis. NSCLC samples were grouped into squamous cell carcinoma (SCC, n=11) and adenocarcinoma (AC, n=11) samples.
Project description:The functions of EGR1, a multifunctional transcription factor, in prostate cancer are well documented. However, little is known about the functions of EGR1 in lung cancer. we observed the function of EGR1 in non-small cell lung carcinoma (NSCLC) and identified the genes that influence cell fate and tumor development. We used microarrays to detail the global programme of gene expression and identified genes differentially expressed when EGR1-overexpressed. We have demonstrated that EGR1 is able to increase cell apoptosis, and inhibit metastasis. And we sought to find genes distributed to decrease the malignancy of human non-small cell lung cancer regulated by EGR1. To that end, H1299 cells were transfected either EGR1 or pcDNA3.1. After 48h, cells were collected for RNA extraction and hybridization on Affymetrix microarrays (PEGR1 VS PCDNA3.1).
Project description:Non-small cell lung cancer (NSCLC) remains one of the leading causes of death worldwide, and thus, new molecular targets need to be identified to improve treatment efficacy. Enhanced TFAP2C expression was found in lung cancer patient tissues and lung cancer cell lines, and its overexpression promoted cell proliferation and cell cycle progression. We conducted microarrays to find the possible downstream effectors regulated by TFAP2C which could play key roles in lung tumorigenesis. Two total RNA samples, extracted from NCI-H292 cells treated with or without TFAP2C siRNA, were analyzed by Affymetrix microarray.
Project description:Non-small cell lung cancer (NSCLC) remains one of the leading causes of death worldwide, and thus, new molecular targets need to be identified to improve treatment efficacy. Enhanced TFAP2C expression was found in lung cancer patient tissues and lung cancer cell lines, and its overexpression promoted cell proliferation and cell cycle progression. We conducted microarrays to find the possible downstream effectors regulated by TFAP2C which could play key roles in lung tumorigenesis.
Project description:The composition and remodelling of the extracellular matrix (ECM) are important factors in the development and progression of cancers, and the ECM is implicated in promoting tumour growth and restricting anti-tumour therapies through multiple mechanisms. The characterisation of differences in ECM composition between normal and diseased tissues may aid in identifying novel diagnostic markers, prognostic indicators and therapeutic targets for drug development. Using tissue from non-small cell lung cancer (NSCLC) patients undergoing curative intent surgery, we characterised quantitative tumour-specific ECM proteome signatures by mass spectrometry, identifying 161 matrisome proteins differentially regulated between tumour tissue and nearby non-malignant lung tissue. We defined a collagen hydroxylation functional protein network that is enriched in the lung tumour microenvironment. We validated two novel putative extracellular markers of NSCLC, the collagen cross-linking enzyme peroxidasin and a disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16), for discrimination of malignant and non-malignant lung tissue. These proteins were up-regulated in lung tumour samples, and high PXDN and ADAMTS16 gene expression was associated with shorter survival of lung adenocarcinoma and squamous cell carcinoma patients, respectively. These data reveal tumour matrisome signatures in human NSCLC.