Project description:Lung tumors, as well as normal tumor-adjacent (NTA) tissue of non-small cell lung cancer (NSCLC) patients, were collected and subjected label-free quantitation shotgun proteomics in data-independent mode to identify differences between the tumors and adjacent tissue. By employing in-depth proteomics, we identified several pathways that are up- or downregulated in the tumors of non-small cell lung cancer patients.
Project description:Immunotherapy has improved the prognosis of patients with advanced non-small cell lung
cancer (NSCLC), but only a small subset of patients achieved clinical benefit. The purpose of our study was to integrate multidimensional data using a machine learning method to predict the therapeutic efficacy of immune checkpoint inhibitors (ICIs) monotherapy in patients with advanced NSCLC.The authors retrospectively enrolled 112 patients with stage IIIB-IV NSCLC receiving ICIs monotherapy. The random forest (RF) algorithm was used to establish efficacy prediction models based on five different input datasets, including precontrast computed tomography (CT) radiomic data, postcontrast CT radiomic data, combination of the two CT radiomic data, clinical data, and a combination of radiomic and clinical data. The 5-fold cross-validation was used to train and test the random forest classifier. The performance of the models was assessed according to the area under the curve (AUC) in the receiver operating characteristic (ROC) curve. Among these models(RF MLP LR XGBoost), our reproduced onnx models have better performance, especially for random forest. The response variable with a value (1/0) indicates the (efficacy/inefficacy) of PD-1/PD-L1 monotherapy in patients with advanced NSCLC
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.
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), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (Squamous cell carcinoma), aC (AC) and large-cell carcinoma (Large cell carcinoma). The aim of this study was to gain a systems biology insight into the current clinical classification. Patients and Methods: Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC. Using integrated systems biology approches, we sought to find out if combining data types from different levels of biology would improve clinical assessment of NSCLC. Results: At both DNA, RNA and miRNA levels we could identify molecular markers that discriminated significantly between the various clinicopathological entities of NSCLC. Conclusions: We report proofs of distinct molecular profiles that contribute to distinguishing NSCLC tumor subtypes even in small biopsies. The246 miRNA experiments have been made in single color with Agilent Human Genome miRNA 15K arrays v3 (design 021827).
Project description:Expression profiles of 18,175 unique genes and three major genetic changes, p53, EGFR and K-ras, were investigated in 149 patients with non-small cell lung cancer (NSCLC), including 90 patients with adenocarcinomas (AD) to determine their relationships with various clinicopathologic features and Gene Ontology (GO) terms. Keywords: Disease state analysis Expression profiles in 149 patients with NSCLC, 9 patients with SCLC and 5 for normal lung tissue.
Project description:In addition to the generation and analysis of metabolomics data on cell lines, samples of normal lung tissue, adenocarcinoma lung tissue and small cell lung carcinoma tissue (seven samples/group) were processed and evaluated metabolite profile differences under the scope of the pilot and feasibility study. These data can be correlated to the metabolite profiles defined in the SCLC and NSCLC cell lines and integrated with the ABPP-determined metabolic kinases to identify distinct metabolic signatures or biomarkers (?oncometabolites?) that distinguish small cell lung cancer from non-small cell lung cancer.
Project description:Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. As miRs are relatively stabile and measurable in both tissue and serum, they are potential prognostic and predictive markers. In this study we aimed to identify significant altered miRs related to angiogenesis in NSCLC From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed.
Project description:Epigenetic changes largely contribute to the regulation of gene expression in cancer cells. DNA methylation is part of the epigenetic gene regulation complex which is relevant for the pathogenesis of cancer. We performed a genome-wide search for methylated CpG islands in tumors and corresponding non-malignant lung tissue samples of 101 stage I-III non-small cell lung cancer (NSCLC) patients by combining methylated DNA immunoprecipitation and microarray analysis using NimbleGenM-BM-4s 385K Human CpG Island plus Promoter arrays. By testing for differences in methylation between tumors and corresponding non-malignant lung tissues, we identified 298 tumor-specifically methylated genes. From many of these genes epigenetic regulation was unknown so far. Gene Ontology analysis revealed an over-representation of genes involved in regulation of gene expression and cell adhesion. Expression of 182 of 298 genes was found to be upregulated after 5-aza-2M-BM-4-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) treatment of 3 NSCLC cell lines by Affymetrix microarray analysis. In addition, methylation of selected genes in primary NSCLCs and corresponding non-malignant lung tissue samples were analyzed by methylation-sensitive high resolution melting analysis (MS-HRM). Our results obtained by MS-HRM analysis confirmed our data obtained by MeDIP-chip analysis. Moreover, by comparing methylation results from MeDIP-chip analysis with clinico-pathological parameters of the patients we observed methylation of HOXA2 as potential parameter for shorter disease-free survival of NSCLC patients. In conclusion, using a genome-wide approach we identified a large number of tumor-specifically methylated genes in NSCLC patients. Our results stress the importance of DNA methylation for the pathogenesis of NSCLCs. Overall, samples of 3 untreated, with Aza-dC treated and with Aza-dC/TSA treated NSCLC cell lines were hybridized to Affymetrix HG-U133_plus_2.0 microarrays (18 in total).
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.