Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA149025 | ENA |
REPOSITORIES: ENA
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Project description:The delicate interaction between cancer cells and the surrounding stroma plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer. A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened utilising the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern. The corresponding antibodies were applied on a tissue microarray, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99was associated with good prognosis in the univariate (p=0.037) and multivariate (p=0.039) analyses. The association was independent from the total proportion of tumour stroma, the fraction of inflammatory cells, and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p=0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The result supports the concept that stromal properties have a significant impact on tumourigenesis. Tissue from five tumors were compared to corressponding microdissected tissue from the same tissue sample
2012-06-05 | E-GEOD-33363 | biostudies-arrayexpress
Project description:The delicate interaction between cancer cells and the surrounding stroma plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer. A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened utilising the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern. The corresponding antibodies were applied on a tissue microarray, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99was associated with good prognosis in the univariate (p=0.037) and multivariate (p=0.039) analyses. The association was independent from the total proportion of tumour stroma, the fraction of inflammatory cells, and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p=0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The result supports the concept that stromal properties have a significant impact on tumourigenesis.
2012-06-06 | GSE33363 | GEO
Project description:Through multidimensional genomic/protein multiomics analysis and clinical information integration of cancer tissue samples, a prognostic method for lung cancer, including non-small cell lung cancer (NSCLC), is developed and applied to precision medical care after discovering new drug targets.
2024-11-01 | PXD053903 | JPOST Repository
Project description:Through multidimensional genomic/protein multiomics analysis and clinical information integration of cancer tissue samples, a prognostic method for lung cancer, including non-small cell lung cancer (NSCLC), is developed and applied to precision medical care after discovering new drug targets.
2024-11-01 | PXD053921 | JPOST Repository
Project description:Through multidimensional genomic/protein multiomics analysis and clinical information integration of cancer tissue samples, a prognostic method for lung cancer, including non-small cell lung cancer (NSCLC), is developed and applied to precision medical care after discovering new drug targets.
2024-11-01 | PXD053969 | JPOST Repository
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]
2011-04-08 | E-GEOD-22874 | biostudies-arrayexpress
Project description:Background: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multi-gene signatures in clinical practice is unclear and the biological importance of individual genes is difficult to assess as the published signatures virtually do not overlap. Methods: Here we describe a novel single institute cohort, including 196 non-small lung cancer (NSCLC) cases with clinical information and long-term follow-up, which was used as a training set to screen for single genes with prognostic impact. The top 450 gene probe sets identified using a univariate Cox regression model (significance level p<0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n=860). Results: The meta-analysis revealed that 17 probe sets were significantly associated with survival (p<0.0005) with a false discovery rate of 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on a tissue microarray including 355 NSCLC samples. Low CADM1 protein expression was associated with shorter survival (p=0.028), with particular influence in the adenocarcinoma patient subgroup (p=0.002). Conclusions: We were able to validate single genes with independent prognostic impact using a novel NSCLC cohort together with a meta-analysis approach. CADM1 was identified as an immunohistochemical marker with a potential application in clinical diagnostics. Fresh frozen tissue of 196 consecutive NSCLC patients, operated between 1995 and 2005 were analyzed using Affymetrix microarrays HG-U133-Plus2. Clinical data were retrieved from the regional lung cancer registry.
2012-10-12 | E-GEOD-37745 | biostudies-arrayexpress
Project description:Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1500 Da) were measured in urine collected from 469 lung cancer patients and 536 population controls using unbiased liquid chromatography-mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further validated in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared to the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA), were each significantly (P <0.00001) elevated in non–small cell lung cancer (NSCLC) and associated with worse prognosis (hazard ratio (HR) =1.81 [P =0.0002], and 1.54 [P =0.025], respectively). Creatine riboside was the strongest classifier of lung cancer status in all and stage I–II cases, important for early detection, and also associated with worse prognosis in stage I–II lung cancer (HR =1.71, P =0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 – 0.99. Both metabolites were significantly (P <0.03) enriched in tumor tissue compared to adjacent non-tumor tissue (N =48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis.
2014-05-06 | MTBLS28 | MetaboLights