Project description:Non-small cell lung cancer (NSCLC) can be classified into the major subtypes adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes. Although explicit molecular, histological and clinical characteristics have been reported for both subtypes, no specific therapy exists so far. However, the characterization of suitable molecular targets holds great promises to develop novel therapies in NSCLC. In the present study, global gene expression profiling of 58 human high grade NSCLC specimens revealed large transcriptomic differences between AC and SCC subtypes: More than 1.700 genes were found to be differentially expressed. Experiment Overall Design: The NSCLC patient collective was composed of the histological subtype adenocarcinoma (n=40) and squamous cell carcinoma (n=18). We subjected gene expression profiles of 40 AC and 18 SCC samples into further analysis. Unsupervised hierarchical clustering of all 58 NSCLC tumors using the 500 most variably expressed transcripts revealed two different clusters, which were strongly associated with the histological subtypes AC and SCC of NSCLC. Our result indicated that the major impact on global transcriptional changes was due to the NSCLC histology.
Project description:Squamous cell lung cancer (SCC) and adenocarcinoma are the most common subtypes of the lung tumours. The search for cancer-directed treatments has increased the need for understanding molecular features of either histological subtype. The aim of this study was to identify transcriptional regulation differences due to miRNA expression profiles between SCC and adenocarcinoma. For this propose, a total of 44 patients were evaluated to assess the correlation between the miRNA and messenger RNA (mRNA) expression levels. Total RNA were isolated, amplified, labeled and hybridized on Agilent human whole genome V2 22 K microarray chip. qRT-PCR was conducted to validate our microarray data. MicroRNA expression was detected and quantified using the TaqMan Low Density Arrays. Predicted miRNA-mRNA interactions were taken from miRanda, miRWalk and TargetScan. After processing data, changes in 56 mRNAs as well as in 9 miRNAs were detected between SCC and adenocarcinoma. Nearly 20% of overall deregulated genes were targeted by at least one of the 9 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a, miR-483-5p, miR-494, miR-601 and miR-708) differentially expressed between SCC and adenocarcinoma. Genes predicted (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) to be targeted by several miRNAs were individually validated by qRT-PCR. We found genes involved in tight junctions and other involved in resistance to anticancer agents. These genes were reliable biomarkers, with high sensitivity and specificity, to detect differences between the two most common histological subtypes of lung cancer. In conclusion, our data demonstrate that the transcriptional regulation differences through miRNA expression play an important role in key hallmarks of non-small cell lung cancer. Identification of new molecular markers in lung carcinoma 44 tumour samples following surgical resection for clinical early stage NSCLC (SCC and adenocarcinoma) This series represents the mRNA profiling only (not miRNA). The related miRNA data are in Series GSE43000.
Project description:Non-small cell lung cancer (NSCLC) can be classified into the major subtypes adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes. Although explicit molecular, histological and clinical characteristics have been reported for both subtypes, no specific therapy exists so far. However, the characterization of suitable molecular targets holds great promises to develop novel therapies in NSCLC. In the present study, global gene expression profiling of 58 human high grade NSCLC specimens revealed large transcriptomic differences between AC and SCC subtypes: More than 1.700 genes were found to be differentially expressed. Keywords: disease subtype analysis
Project description:To identify microRNAs that regulate therapeutic resistance, we conducted a high-throughput miRNA microarray on a cohort study of primary NSCLC (non-small cell lung cancer) tissues and adjacent normal tissues. We found some microRNAs related to therapeutic resistance and poor prognosis. In this study, the patients who were diagnosed with resected NSCLC (adenocarcinoma or squamous cell carcinoma) were enrolled. All tumors were reviewed by pathologists and were pathologically diagnosed according to the World Health Organisation Classification of Tumors. Twenty-nine patients who received four or more courses of first-line platinum-based chemotherapy after postoperative recurrence were divided into two groups (responder (n=17) and non-responder group (n=12)). As identified by ANOVA analysis and quantitative RT-PCR (qRT-PCR) of 4 groups, some miRNAs exhibited significant expression changes.
Project description:We performed a pilot proteogenomic study to compare lung adenocarcinoma to lung squamous cell carcinoma using quantitative proteomics (6-plex TMT) combined with a customized Affymetrix GeneChip. Using MaxQuant software, we identified 51,001 unique peptides that mapped to 7,241 unique proteins and from these identified 6,373 genes with matching protein expression for further analysis. We found a minor correlation between gene expression and protein expression; both datasets were able to independently recapitulate known differences between the adenocarcinoma and squamous cell carcinoma subtypes. We found 565 proteins and 629 genes to be differentially expressed between adenocarcinoma and squamous cell carcinoma, with 113 of these consistently differentially expressed at both the gene and protein levels. We then compared our results to published adenocarcinoma versus squamous cell carcinoma proteomic data that we also processed with MaxQuant. We selected two proteins consistently overexpressed in squamous cell carcinoma in all studies, MCT1 (SLC16A1) and GLUT1 (SLC2A1), for further investigation. We found differential expression of these same proteins at the gene level in our study as well as in other public gene expression datasets. These findings combined with survival analysis of public datasets suggest that MCT1 and GLUT1 may be potential prognostic markers in adenocarcinoma and druggable targets in squamous cell carcinoma.
Project description:The aim of this study is to generate and validate biomarkers to stratify patients with Barrett’s esophagus in terms of risk for developing cancer. We studied gene expression profiling in 69 frozen specimens, consisting of esophageal squamous epithelium from 19 healthy subjects, 20 specimens from patients with Barrett’s esophagus and 21 cases of esophageal adenocarcinoma, 9 cased of esophageal squamous cell carcinoma by whole genome microarray analysis. Laser capture microdissection technique was applied to procure cells from defined regions of Barrett’s esophagus metaplasia and esophageal adenocarcinoma. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent cohort consisting of 42 cases. Furthermore, immunohistochemistry was performed using antibodies to two selected target molecules on a third independent cohort of 36 specimens, consisting of 36 cases. A total of 1176 genes were associated significantly with esophageal adenocarcinoma. The expression pattern of a 4 gene signature with the highest discriminant score based on linear discriminant analysis (GeneSpring GX10.2), was identified and validated by qRT-PCR in independent cohort. Gene expression profiling of 20 specimens of Barrett's esophagus patients, 21 specimens of adenocarcinoma patients and 19 biopsies from patients with normal esophageal squamous epithelium, 9 specimens of squamous cell carcinoma were studied.
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.