Project description:Gene expression differences between between matched tumor and normal samples were analyzed using paired t-test. Keywords: disease state analysis
Project description:Introduction: Macrophage phenotype in the tumor microenvironment correlates with prognosis in non-small cell lung cancer (NSCLC). Immunosuppressive macrophages promote tumor progression, while pro-inflammatory macrophages may drive an anti-tumor immune response. How individual NSCLCs impact macrophage phenotype is a major knowledge gap. Methods: To systematically study the impact of lung cancer cells on macrophage phenotypes, we developed an in vitro co-culture model comprised of molecularly and clinically-annotated patient-derived NSCLC lines, human cancer-associated fibroblasts, and murine macrophages. Induced macrophage phenotype was studied through qRT-PCR and validated in vivo using NSCLC xenografts through quantitative immunohistochemistry and clinically with TCGA “matched” patient tumors. Results: 72 NSCLC cell lines were studied. The most frequent highly induced macrophage-related gene was Arginase-1, reflecting an immunosuppressive M2-like phenotype. This was independent of multiple clinicopathologic factors, which also did not impact M2:M1 ratios in matched TCGA samples. In vivo, tumors established from high Arginase-1-inducing lines (Arghi) had a significantly elevated density of Arg1+ macrophages. Matched TCGA clinical samples to Arghi NSCLC lines had a significantly higher ratio of M2:M1 macrophages. Conclusions: In our preclinical model, a large panel of patient-derived NSCLC lines most frequently induced high expression Arginase-1 in co-cultured mouse macrophages, independent of major clinicopathologic and oncogenotype-related factors. Arghi cluster-matched TCGA tumors contained a higher ratio of M2:M1 macrophages. Thus, this preclinical model reproducibly characterizes how individual NSCLCs modulate macrophage phenotype, correlates with macrophage polarization in clinical samples, and can serve as an accessible platform for further investigation of macrophage-specific therapeutic strategies.
Project description:Transcriptomic profiling of metastatic NSCLC cancer patients from tumor tissue and organ-matched normal tissue as reference which were taken as part of the WINTHER clinical trial. The organ-matched normal tissues were used in order to eliminate host gene expression variability while discarding most genetic variability between individuals. The goal was to trial was to navigate patients to therapy on the basis of fresh biopsy-derived DNA sequencing or RNA expression
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:To identify lncRNA expression in placentas from patients with late-onset preeclampsia (LOPE), we have employed whole genome microarray expression profiling as a discovery platform to identify differential expression of lncRNAs in placental samples from LOPE patients and normal controls. For microarray analysis, 8 randomly and blindly selected placental samples from LOPE patients and matched controls (4 samples per group) were used to extract total RNA. The expression profiles of the placental lncRNAs were detected using the Agilent Human lncRNA Microarray V4.0(OE Biotech, Shanghai, China). The threshold for a dysregulated lncRNA was set as a fold-change (FC) value of 2.0 or greater. A totle of 163 differentially expressed lncRNAs were identified. Expression of nine lncRNAs (NONHSAT145880, ENST00000587240, NONHSAT116812, NONHSAT104536, FR339600, NONHSAG018907, TCONS_l2_00014782, NONHSAT134432 and NONHSAG024318) from this microarray was quantified n placental tissues from the LOPE patients (n = 40) and controls (n = 35) delivered by caesarean section by real-time PCR, confirming low variability between the qRT-PCR results and the microarray data.
Project description:Plasma samples from 100 early stage (I to IIIA) non–small-cell lung cancer (NSCLC) patients and 100 non-cancer controls were screened for 754 circulating microRNAs via qRT-PCR, using TaqMan MicroRNA Arrays. Our objective was to identify a panel of circulating microRNAs in plasma that will contribute to early detection of lung cancer.