Project description:Small cell lungcancer (SCLC) is an aggressive malignancy with dismal clinical outcomes, due inpart to the scarcity of post-relapse tissue samples. To understand more of transcriptional changes associated with treatment resistance, we performed RNAseq analysis of 61 SCLC cell lines.
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:SCLC is molecularly and immunologically heterogenous. Here, using transcriptional and epigenomic profiling of plastic SCLC states in human and mouse cell lines, and patient samples, we define the phenotype of a SCLC population marked by increased MHC Class I antigen presentation.
Project description:Drug-tolerant persister cells withstand treatments by adapting their identity through lineage-dependent plasticity during systemic anti-cancer therapies. This phenomenon is evident in small-cell lung carcinoma (SCLC), a lethal neuroendocrine cancer initially responsive (60-80%) to platinum-based chemotherapy but succumbing to resistance within 6 months in advanced stages. This resistance associates with the transdifferentiation of residual tumour cells into a non-neuroendocrine state, a process intricately tied to SCLC's chemotolerance, yet molecular mechanisms governing this lineage conversion remain completed understood. Here we use paired cytoplasmic RNA-seq and polysomal RNA-seq to compare gene expression between NE and non-NE SCLC cell lines on both transcriptional and translational level. We report that first-line chemotherapy induces translation initiation factor eIF6 in drug-tolerant persister-like cells in SCLC, correlating with the non-neuroendocrine state in SCLC. Intervening eIF6 inhibits non-neuroendocrine transdifferentiation, thus enhancing SCLC responsiveness to chemotherapy. This study sheds light on eIF6's potential therapeutic interventions to mitigate treatment resistance in SCLC.
Project description:Aim: To determine the miRNA expression profile of SCLC cell lines vs. normal lung tissue. Keywords: disease state analysis Total RNA isolated from SCLC cell lines H69, HTB-172, HTB-173 and HTB-184 were compared to a mixed RNA sample derived from 6 normal lung tissue samples (fresh surgical material), from 6 tumor-free patients. The same reference sample (normal lung) was used on all 4 microarrays.
Project description:SCLC is molecularly and immunologically heterogenous. Here, using transcriptional and epigenomic profiling of plastic SCLC states in human and mouse cell lines, and patient samples, we define the phenotype of a SCLC population marked by increased MHC Class I antigen presentation.
Project description:SCLC is molecularly and immunologically heterogenous. Here, using transcriptional and epigenomic profiling of plastic SCLC states in human and mouse cell lines, and patient samples, we define the phenotype of a SCLC population marked by increased MHC Class I antigen presentation.