Project description:BACKGROUND: Global gene expression analysis provides a comprehensive molecular characterization of non-small cell lung cancer. The aim of this study was to evaluate the feasibility of integrating expression profiling into routine clinical work-up by including minute bronchoscopic biopsies and develop a robust prognostic gene expression signature METHODS: Tissue samples from a series of 41 chemotherapy-naïve non-small cell lung cancer patients and 15 control patients with inflammatory lung diseases were obtained during routine clinical work-up and gene expression profiles were gained using a highly sensitive oligonucleotide array platform (Novachip ; 34'207 transcripts). Gene expression signatures were analyzed by correlation with histological and clinical parameters and validated on independent published datasets and immunohistochemistry. RESULTS: Tumor tissue classification based on the gene expression results was strongly dependent on the proportion of tumor cells present in the biopsies and showed an overall sensitivity of 80% and specificity of 89%. For prognostication we developed a metagene consisting of 13 genes, which was validated on 4 independent published datasets. The robustness of this metagene has been demonstrated by a virtual independence from tumor cells present in the biopsies. Furthermore, vascular endothelial growth factor-beta, one of the key prognostic genes was validated by immunohistochemistry on 508 independent tumor samples. CONCLUSIONS: The proposed strategy of integrating functional genomics into routine clinical work-up allows molecular tumor classification and prediction of survival in patients with non-small cell lung cancer of all stages and is suitable for an integration in the daily clinical practice. Keywords: Gene expression profiling for disease state analysis in lung cancer patients 56 lung biopsies, 4 different Phenotypes: NSCLC-squa., NSCLC-NOS, NSCLC-Adeno, Ctr.-Infl.
Project description:Background: Non-small cell lung cancers (NSCLCs) consist of adenocarcinoma (ADC), squamous cell carcinoma (SCC) and other types. Since most NSCLCs are now diagnosed from small biopsies or cytology materials, classification is not always accurate. This is a problem as many therapy regimens and clinical trials are histology-dependent. Specific Aim: To develop an RNA expression signature as an adjunct test for routine histo-pathological classification of NSCLCs. Methods: A microarray dataset of resected ADC and SCC cases was used as the learning set for an ADC-SCC signature. The Cancer Genome Atlas (TCGA) lung RNAseq dataset was used as a validation set. Another microarray dataset of ADCs and non-malignant lung was used as the learning set for a Tumor-Nonmalignant signature. The classifiers were selected as the most differentially expressed genes and sample classification was determined by a nearest distance approach. Results: We developed a 42-gene expression signature that contained many genes used in immunostains for NSCLC typing. Testing of the TCGA and other public datasets resulted in high accuracies (93-95%). We also observed that most non-malignant lung samples were classified as â??adenocarcinomasâ??, so we added 20 genes to differentiate tumor from non-malignant lung. Together, the 62-gene signature can discriminate ADC, SCC, and non-malignant lung. Additionally, a prediction score was derived that correlated both with histologic grading and survival. Summary and significance: Our histologic classifier provides a non-subjective method to aid in the pathological diagnosis of lung cancer and assist enrollment onto histology-based clinical trials 83 lung adenocarcinomas and 83 matched adjacent non-malignant lung were profiled on Illumina WG6-V3 expression arrays
Project description:BACKGROUND: Global gene expression analysis provides a comprehensive molecular characterization of non-small cell lung cancer. The aim of this study was to evaluate the feasibility of integrating expression profiling into routine clinical work-up by including minute bronchoscopic biopsies and develop a robust prognostic gene expression signature METHODS: Tissue samples from a series of 41 chemotherapy-naïve non-small cell lung cancer patients and 15 control patients with inflammatory lung diseases were obtained during routine clinical work-up and gene expression profiles were gained using a highly sensitive oligonucleotide array platform (Novachip ; 34'207 transcripts). Gene expression signatures were analyzed by correlation with histological and clinical parameters and validated on independent published datasets and immunohistochemistry. RESULTS: Tumor tissue classification based on the gene expression results was strongly dependent on the proportion of tumor cells present in the biopsies and showed an overall sensitivity of 80% and specificity of 89%. For prognostication we developed a metagene consisting of 13 genes, which was validated on 4 independent published datasets. The robustness of this metagene has been demonstrated by a virtual independence from tumor cells present in the biopsies. Furthermore, vascular endothelial growth factor-beta, one of the key prognostic genes was validated by immunohistochemistry on 508 independent tumor samples. CONCLUSIONS: The proposed strategy of integrating functional genomics into routine clinical work-up allows molecular tumor classification and prediction of survival in patients with non-small cell lung cancer of all stages and is suitable for an integration in the daily clinical practice. Keywords: Gene expression profiling for disease state analysis in lung cancer patients
Project description:Background: Non-small cell lung cancers (NSCLCs) consist of adenocarcinoma (ADC), squamous cell carcinoma (SCC) and other types. Since most NSCLCs are now diagnosed from small biopsies or cytology materials, classification is not always accurate. This is a problem as many therapy regimens and clinical trials are histology-dependent. Specific Aim: To develop an RNA expression signature as an adjunct test for routine histo-pathological classification of NSCLCs. Methods: A microarray dataset of resected ADC and SCC cases was used as the learning set for an ADC-SCC signature. The Cancer Genome Atlas (TCGA) lung RNAseq dataset was used as a validation set. Another microarray dataset of ADCs and non-malignant lung was used as the learning set for a Tumor-Nonmalignant signature. The classifiers were selected as the most differentially expressed genes and sample classification was determined by a nearest distance approach. Results: We developed a 42-gene expression signature that contained many genes used in immunostains for NSCLC typing. Testing of the TCGA and other public datasets resulted in high accuracies (93-95%). We also observed that most non-malignant lung samples were classified as “adenocarcinomas”, so we added 20 genes to differentiate tumor from non-malignant lung. Together, the 62-gene signature can discriminate ADC, SCC, and non-malignant lung. Additionally, a prediction score was derived that correlated both with histologic grading and survival. Summary and significance: Our histologic classifier provides a non-subjective method to aid in the pathological diagnosis of lung cancer and assist enrollment onto histology-based clinical trials
Project description:Current clinical therapy of non-small cell lung cancer depends on histo-pathological classification. This approach poorly predicts clinical outcome for individual patients. Proteogenomic characterization analysis holds promise to improve clinical stratification, thus paving the way for individualized therapy. We investigated proteogenomic characterization and performed comprehensive integrative genomic analysis of human large cell lung cancer. Here we analyzed proteomes of 29 paired normal lung tissues and large cell lung cancer, identified significantly deregulated proteins associated with large cell lung cancer.