Project description:Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small cell lung cancer (NSCLC), we compared RNAseq data of 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the CTdatabase, 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase. Cluster analysis revealed that CTA expression is histology-dependent and concurrent expression is common. Immunohistochemistry confirmed tissue specific protein expression of selected genes. Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from the Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer, was not confirmed, neither in our RNAseq-cohort nor in an independent meta-analysis of 1117 NSCLC cases. Fresh frozen tumor tissue from 199 patients diagnosed with NSCLC and surgically treated 2006-2010 at the Uppsala University Hospital, Uppsala, Sweden and 19 paired normal lung tissues. Clinical data were retrieved from the regional lung cancer registry. Several of the new CTAs are poorly characterized Sample characteristics values represent; pTNM: decided by Hans Brunnstrom, pathologist in Lund Spring 2013 Stage according to pTNM: 1=1a 2=1b 3=2a 4=2b 5=3a 6=3b 7=IV Histology diagnosis spring 2013 HB: 1=squamous cell cancer 2=AC unspecified 3=Large cell/ NOS Surgery date: the date when sample arrived at Patologen UAS Age: age when surgery was performed Vital date: day of death or latest contact Dead: 0=no 1= yes Smoking history : 1=current 2=ex >1year 3=never WHO performance status: Performance status 0-4 Please note that the L608T_2122, L771T_1 data columns (in the processed data files) are associated with L608T and L771T samples, respectively.
Project description:Genomic libraries (500 bps) will be generated from total genomic DNA derived from lung cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.
Project description:Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small cell lung cancer (NSCLC), we compared RNAseq data of 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the CTdatabase, 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase. Cluster analysis revealed that CTA expression is histology-dependent and concurrent expression is common. Immunohistochemistry confirmed tissue specific protein expression of selected genes. Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from the Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer, was not confirmed, neither in our RNAseq-cohort nor in an independent meta-analysis of 1117 NSCLC cases.
Project description:To define the hedgehog-interacting protein (Hhip) expression domain in adult mouse lung, we conduct single-cell RNAseq of the mouse lung using 10X scRNAseq technique.
Project description:Even though small cell lung cancer (SCLC) has entered the age of broad genomic analysis, platinum-based chemotherapy remains the standard care for SCLC. Topotecan is the only approved agent for recurrent or progressive SCLC (1). In the absence of well-defined genomic biomarkers, clinical efficacy signals in genomically distinct subsets of SCLC could have been missed. Serine/Arginine Splicing Factor 1 (SRSF1) is a member of SR protein family. The deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers suggest that there are complex mechanisms and pathways underlying SRSF1-mediated transformation (2). Whole exome and transcriptome sequencing of primary tumor SCLC from 99 Chinese patients has identified SRSF1 DNA amplification and mRNA over-expression which predicts poor survival in Chinese SCLC patients. In vitro and in vivo studies have demonstrated that SRSF1 is essential for tumorigenecity of SCLC and plays a key role in DNA repair and chemo-sensitivity. We did RNAseq on 79 small cell lung cancer patients' tumor sample and 7 normal lung tissue. We normalized the RNAseq data and did differential expression analysis. The deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers suggest that there are complex mechanisms and pathways underlying SRSF1-mediated transformation.
Project description:We report RNAseq data from two independent mouse syngeneic lung cancer cell lines LLC and UN-SCC679 in an altered DSTYK context Lung cancer remains the leading cause of cancer-related death worldwide. We identify DSTYK, a dual serine/threonine and tyrosine non-receptor protein kinase, as a novel actionable target altered in non-small cell lung cancer (NSCLC). We also show DSTYK´s association with a lower overall survival (OS) and poorer progression-free survival (PFS) in multiple patient cohorts. To ascertain the potential molecular carcinogenesis processes in which DSTYK was involved, we performed an RNAseq analysis of two different lung cancer cell lines with either overexpressed or inhibited DSTYK. Inhibition was achieved through shRNA technology. These cell lines were cultured in RPMI 1640 supplemented with 10% Fetalclone (Thermo Fisher Scientific) and 100 U/mL penicillin-100 µg/mL streptomycin (Thermo Fisher Scientific). All cells were grown in a humidified incubator containing 5% CO2 at 37°C. Cell lines were routinely tested for mycoplasma.