Project description:A prevalence study was conducted for MET amplification and overexpression in liquid biopsy samples from patients with NSCLC who relapsed on ALK, ROS1 or RET tyrosine kinase inhibitors. MET-mediated resistance was detected in 37.5% of tissue biopsies, which allow the detection of MET overexpression, compared to 7.4% of liquid biopsies. This study highlights the importance of considering MET overexpression as a resistance driver to fusion targeted therapies
Project description:The majority of metastatic clear cell renal cell carcinoma (ccRCC) patients are treated with tyrosine kinase inhibitors (TKIs) in first line, however, a fraction are refractory to these drugs. MicroRNAs (miRNA) are regulatory molecules that have proven to be accurate biomarkers in cancer. Here we identified miRNA predictive of progressive disease under TKI treatment. Whole miRNA expression was quantified by deep-sequencing in a discovery set of 74 metastatic ccRCC cases uniformly treated with TKIs. Twenty nine miRNAs were found to be differentially expressed in the tumors of patients who progressed under TKI therapy. Among six miRNAs selected for validation, an over-expression of miR-1307-3p, miR-155-5p, miR-221-3p, miR-425-5p and miR-222-3p was confirmed in patients with progressive disease as best response. A 2 miRNA-based classifier could discriminate individuals with progressive disease upon TKI treatment with a better predictive value than clinicopathological risk factors commonly used. miRNAs significantly associated with progression-free survival and overall survival were identified, and 7 miRNAs were found to overlap as predictive for early progressive disease, PFS and OS.
Project description:Intrinsic subtyping of breast cancer was performed using an nCounter RUO-PAM50 gene expression assay to determine the ability of instrinsic subtyping to predict what patients may benefit from altered chemotherapy scheduling in the CALGB 9741 clinical trial population. FFPE primary breast tumor samples archived at the CALGB Pathology Coordinating Office (PCO) were used to obtain total RNA for instrinsic subtyping using the nCounter Analysis System. Gene-expression profiles were generated for 1321 of 1471 patient samples (90%) suitable for inclusion in this study.
Project description:In this study, to investigate the underlying molecular mechanisms of how EGFR-TKIs resistance occurs in NSCLC, we examined gene expression using microarray technology on gefitinib-resistant NSCLC cells to obtain differentially expressed (DE) lncRNAs and mRNAs. Then we carried out KEGG enrichment analysis for DE-mRNAs and constructed the ceRNA regulatory network of DE-lncRNAs and DE-mRNAs. Our results revealed the downregulated lncRNA LINC01128 acted as ceRNA to decrease PTEN via sponging miR-25-3p, and then the signal reactions caused by the reduction of PTEN would activate PI3K/Akt signaling pathway, which may lead to the development of drug resistance to EGFR-TKIs in NSCLC. Our findings will provide a novel perspective for the underlying molecular mechanisms of EGFR-TKIs resistance in NSCLC. Besides, this research will help to develop new therapeutic targets for EGFR-TKIs resistance in NSCLC.
2022-01-14 | GSE193628 | GEO
Project description:NGS of patients with ALK, ROS1 and RET fusions progressed to TKIs
Project description:We investigated tumoral miRNA expression of patients with clear-cell renal cell carcinoma treated with VEGFR-TKIs in first line. Sequencing was performed on 109 FFPE resection specimens. The samples were sequenced in 2 major batches (2014 and 2017).
Project description:Via a GWA study, several SNPs have been identified as markers capable of predicting prognosis of lung cancer patients receiving TKIs therapy as first-line treatment. In order to get insights into how these genetic variants are linked to traits of interest, we conducted a genome-wide eQTL study by integrated analyses of SNP genotyping array data and gene expression array data of 115 subjects of lung adenocarcinoma. Our study successfully identified several SNPs as eQTLs, whose genotype were significantly associated with expression levels of several already known genes related to lung cancer.