Unique microRNA profiles in EGFR-mutated lung adenocarcinomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE48414 | GEO | 2014/03/10
SECONDARY ACCESSION(S): PRJNA209985
REPOSITORIES: GEO
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Project description:We have examined the microRNA expression in 154 lung adenocarcinoma samples and 20 paired normal lung tissue samples and investigated the microRNA expression to clinical variables, EGFR- and KRAS- mutational status and time to progression. 174 samples are analyzed. 154 from lung adenocarcinoma tumor tissue and 20 from paired normal lung tissue samples. No replicates or control samples included.
2014-03-10 | E-GEOD-48414 | biostudies-arrayexpress
Project description:We have examined the microRNA expression in 154 lung adenocarcinoma samples and 20 paired normal lung tissue samples and investigated the microRNA expression to clinical variables, EGFR- and KRAS- mutational status and time to progression. 174 samples are analyzed. 154 from lung adenocarcinoma tumor tissue and 20 from paired normal lung tissue samples. No replicates or control samples included.
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Project description:The findings of mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor, and we need to know more about the genetic and epigenetic alterations in lung cancer. MicroRNAs are involved in crucial biological processes like carcinogenesis by regulating gene expression at the post-transcriptional level. In this project, we have studied the microRNA expression of lung adenocarcinomas and corresponding normal lung tissue and correlated the expression with clinical data and EGFR- and KRAS-mutational status. Agilent microarrays have been used, examining microRNA expression in 154 surgically resected lung adenocarcinomas and 20 corresponding normal lung tissue samples. Findings were confirmed by RT-qPCR in the same cohort and in an independent cohort of 103 lung cancer patients. EGFR and KRAS mutation analyses were also performed. 129 microRNAs were significantly differentially expressed in lung adenocarcinomas compared with normal lung tissue, and 17 microRNAs were differentially expressed between EGFR-mutated and EGFR wildtype tumors. We identified microRNAs associated with time to progression. We have identified several aberrantly expressed microRNAs that discriminate lung adenocarcinomas from normal lung tissue, and hence may be potential biomarkers for early detection. We have found microRNAs that are differentially expressed between EGFR-mutated and EGFR wildtype lung adenocarcinomas, suggesting that microRNAs can be used as molecular biomarkers in classification. We hypothesize that microRNA expression can be used as biomarkers for clinical course.
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Project description:Using the highly sensitive miRNA array, we determined the serum miRNAs profiles of 10 non-smokers, 10 smokers and 10 lung cancer patients by miRCURY LNA™ microRNA Arrays. Differential expressed miRNAs were further validated in a larger scale samples. We found that let-7i-3p and miR-154-5p were significantly downregulation in serum of smokers and lung cancer patients. The serum level of let-7i-3p and miR-154-5p is associated with smoking and smoking-related lung cancer.
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Project description:Cancer precision medicine largely relies on knowledge about genetic aberrations in tumors and next-generation-sequencing studies have shown a high mutational complexity in many cancers. Although a large number of the observed mutations is believed to be not causally linked with cancer, the functional effects of many rare mutations but also of combinations of driver mutations are often unknown. Here, we perform a systems analysis of a model of EGFR-mutated non-small cell lung cancer resistant to targeted therapy that integrates whole exome sequencing, global time-course discovery phosphoproteomics and computational modeling to identify functionally relevant molecular alterations. Our approach allows for a complexity reduction from over 2,000 genetic events potentially involved in mediating resistance to only 44 phosphoproteins and 35 topologically close genetic alterations. We perform single- and combination-drug testing against the predicted phosphoproteins and discovered that targeting of HSPB1, DBNL and AKT1 showed potent anti-proliferative effects overcoming resistance against EGFR-inhibitory therapy. Our approach may therefore be used to complement mutational profiling to identify functionally relevant molecular aberrations and propose combination therapies across cancers.
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Project description:We have examined the both miRNA and mRNA expression profiles in 155 lung adenocarcinoma samples with known EGFR mutation status (52 mutated and 103 wild-type cases). An integrative analysis was performed to identify the unique miRNA-mRNA regulatory network in EGFR-mutated lung adenocarcinoma.
2018-11-13 | GSE119268 | GEO
Project description:We have examined the both miRNA and mRNA expression profiles in 155 lung adenocarcinoma samples with known EGFR mutation status (52 mutated and 103 wild-type cases). An integrative analysis was performed to identify the unique miRNA-mRNA regulatory network in EGFR-mutated lung adenocarcinoma.
2018-11-13 | GSE119267 | GEO
Project description:We investigated the significance of MUC21 in EGFR-mutated lung adenocarcinoma (LADC). Two-hundred forty-one surgically resected LADCs (116 EGFR-mutated and 125 wild-type tumors) were examined for immunohistochemical expression of MUC21 protein. A polyclonal antibody and two monoclonal antibodies (heM21C and heM21D) that bind differentially glycosylated MUC21 epitopes were used, and MUC21 proteins detected by these antibodies were named MUC21P, MUC21C, and MUC21D, respectively. MUC21 mRNA levels were semi-quantified and classified into "high" and "low". Among the immunohistochemical expression detected by three different antibodies, high expressors tended to be related to EGFR mutations. The three varieties of the immunohistochemical expressions were related to different histological elements in the EGFR-mutated LADCs. Either MUC21P or MUC21C high expressors had a higher proportion of lepidic elements with low papillary structure and micropapillary elements. MUC21D high expressors had a significantly higher proportion of micropapillary elements (Mann-Whitney test P ≤0.0001). Furthermore, MUC21D high expressors showed high incidence of lymphatic canal invasion and lymph node metastasis (Pearson x2 test, P = 0.0021, P = 0.0125), and a significantly higher recurrence rate (5-year recurrence-free survival 50.7% vs. 73.8%, log-rank test P = 0.0495). MUC21 proteins with a specific glycosylation status may be involved in the progression of EGFR-mutated LADCs, particularly at the stage where tumors are transforming from pure lepidic to micropapillary through low papillary lepidic lesions.
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Project description:The EGFR gene was one of the first molecules to be selected for targeted gene therapy. EGFR-mutated lung adenocarcinoma, which is responsive to EGFR inhibitors, is characterized by a distinct oncogenic pathway in which unique microRNA (miRNA)⁻mRNA interactions have been observed. However, little information is available about the miRNA⁻mRNA regulatory network involved. Both miRNA and mRNA expression profiles were investigated using microarrays in 155 surgically resected specimens of lung adenocarcinoma with a known EGFR mutation status (52 mutated and 103 wild-type cases). An integrative analysis of the data was performed to identify the unique miRNA⁻mRNA regulatory network in EGFR-mutated lung adenocarcinoma. Expression profiling of miRNAs and mRNAs yielded characteristic miRNA/mRNA signatures (19 miRNAs/431 mRNAs) in EGFR-mutated lung adenocarcinoma. Five of the 19 miRNAs were previously listed as EGFR-mutation-specific miRNAs (i.e., miR-532-3p, miR-500a-3p, miR-224-5p, miR-502-3p, and miR-532-5p). An integrative analysis of miRNA and mRNA expression revealed a refined list of putative miRNA⁻mRNA interactions, of which 63 were potentially involved in EGFR-mutated tumors. Network structural analysis provided a comprehensive view of the complex miRNA⁻mRNA interactions in EGFR-mutated lung adenocarcinoma, including DUSP4 and MUC4 axes. Overall, this observational study provides insight into the unique miRNA⁻mRNA regulatory network present in EGFR-mutated tumors. Our findings, if validated, would inform future research examining the interplay of miRNAs and mRNAs in EGFR-mutated lung adenocarcinoma.
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Project description:This was a collaborative study to discover somatic mutations in 188 lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are likely to play a role in carcinogenesis. The observed mutational profiles correlate with clinical features, smoking status, and DNA repair defects. These results are complemented by data integration including SNP array data and gene expression array data (deposited here). Our findings shed further light on several key signaling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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