Expression data of microRNAs from human lung cancer at different clinical types
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE186666 | GEO | 2021/11/12
REPOSITORIES: GEO
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Project description:Metastatic relapse from treatment failure has been a formidable challenge to finding a cure for EGFR-mutant lung cancer. Metastasis to the brain is a severe complication for 45% of patients with EGFR-mutant lung cancer that drastically reduces their quality of life and survival. Here, we demonstrate that genetic inhibition of S100A9, ALDH1A1, RAR, or pharmacological inhibition of the RA pathway using pan-RAR inhibitors significantly reduces brain relapse from osimertinib-refractory cancer cells. Our study has therefore revealed a novel S100A9-ALDH1A1-RA signaling axis in the EGFR-mutant lung cancer cells that drives osimertinib-refractory metastatic brain relapse and identified a potential vulnerability in lung cancer cells that can be therapeutically targeted to prolong progression-free survival in EGFR-mutant lung cancer patients.
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Project description:Brain metastasis is one of the most feared complications of cancer and the most common intracranial malignancy in adults. Its underlying mechanisms remain unknown. From breast cancer patients with metastatic disease we isolated cell populations that aggressively colonize the brain. Transcriptomic analysis of these cells yielded overlapping gene sets whose expression is selectively associated with brain metastasis. The expression of seventeen of these genes in primary breast tumors is associated with brain relapse in breast cancer patients. Some of these genes are also associated with metastasis to lung but not to liver, bone or lymph nodes, providing a molecular basis for the long-observed link between brain and lung metastasis. Among the functionally validated brain metastasis genes, the cyclooxigenase COX-2, the EGFR ligand HB-EGF, and the brain-specific 2-6 sialyltransferase ST6GALNAC5 mediate cancer cell passage through the blood-brain barrier. Other brain metastasis genes encode inflammatory factors and brain-specific proteolytic regulators, suggesting a multifaceted program for breast cancer colonization of the brain. Experiment Overall Design: 204 primary tumors from breast cancer patients with known site of relapse were studied, focussing on brain relapse versus other relapse. Identified genes were validated in this cohort.
2009-06-23 | E-GEOD-12276 | biostudies-arrayexpress
Project description:Expression data of microRNAs from human lung cancer at different clinical types
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Project description:Varicella pneumonia is the most common and severe complication of primary varicella-zoster virus (VZV) infection in adults. Pathogenesis of varicella pneumonia is largely unknown, mainly due to limited availability of clinical specimens and lack of appropriate VZV animal models. Simian varicella virus (SVV) infection of nonhuman primates closely recapitulates clinical and pathogenic features of human VZV disease. This study aimed to elucidate the virus and host factors that contribute to the pathogenesis of varicella pneumonia. The deposited data present changes in gene expression in the lung of SVV-infected cynomolgus macaques (Macaca fascicularis) at 3, 6 and 9 days after infection, and mock-infected control macaques at 3 days after infection.
2020-09-01 | E-MTAB-8485 | biostudies-arrayexpress
Project description:Brain metastasis is one of the most feared complications of cancer and the most common intracranial malignancy in adults. Its underlying mechanisms remain unknown. From breast cancer patients with metastatic disease we isolated cell populations that aggressively colonize the brain. Transcriptomic analysis of these cells yielded overlapping gene sets whose expression is selectively associated with brain metastasis. The expression of seventeen of these genes in primary breast tumors is associated with brain relapse in breast cancer patients. Some of these genes are also associated with metastasis to lung but not to liver, bone or lymph nodes, providing a molecular basis for the long-observed clinical link between brain and lung metastasis. Among the functionally validated brain metastasis genes, the cyclooxygenase COX-2, the EGFR ligand HB-EGF, and the brain-specific α2-6 sialyltransferase ST6GALNAC5 mediate cancer cell passage through the blood-brain barrier. Other brain metastasis genes encode inflammatory factors and brain-specific proteolytic regulators, suggesting a multifaceted program for breast cancer colonization of the brain. Experiment Overall Design: Two different breast cancer cell lines, MDA-MB-231 and freshly isolated pleural effusion CN34 were used in this study. The MDA-MB-231 group contains three biological replicates of the parental, unselected population, and 4 brain metastatic isolates. CN34 contains 2 biological replicates of the parental, unselected population, and 4 brain metastatic isolates. In each case, the parental population was compared to the brain metastatic isolates to identify gene expression changes associated with the brain metastatic phenotype.
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2016-07-03 | E-GEOD-52050 | biostudies-arrayexpress
Project description:Lung cancer is the leading cause of cancer death worldwide. Brain metastasis is a major cause of morbidity and mortality in lung cancer. CDH2 (N-cadherin, a mesenchymal marker in epithelial-mesenchymal transition) and ADAM9 (a member of type I transmembrane proteins) have been reported relating to lung cancer brain metastasis, however, it is still not clear whether any interaction between them to mediate lung cancer brain metastasis. Since microRNAs were discovered to regulate many biological functions and disease processes (e.g., cancer) by down-regulating their target genes, microRNA microarrays were used to identify ADAM9 regulated miRNAs that target CDH2 in aggressive lung cancer cells. Luciferase assays and immunoblotting proved that CDH2 was a target gene of miR-218. The expression of miR-218 was generated from pri-mir-218-1, located in SLIT2, in low invasive lung adenocarcinoma while it was inhibited in aggressive lung adenocarcinoma. Down-regulation of ADAM9 could up-regulate SLIT2 and miR-218, thus down-regulate CDH2 expression. This study elucidated the mechanism of ADAM9 activating CDH2 may be due to release the inhibition of miR-218 on CDH2 in lung adenocarcinoma. For each of the cell lines bm#2, bm#7, and F4, one microarray was analyzed.
2016-07-03 | E-GEOD-51833 | biostudies-arrayexpress
Project description:Brain metastasis is one of the most feared complications of cancer and the most common intracranial malignancy in adults. Its underlying mechanisms remain unknown. From breast cancer patients with metastatic disease we isolated cell populations that aggressively colonize the brain. Transcriptomic analysis of these cells yielded overlapping gene sets whose expression is selectively associated with brain metastasis. The expression of seventeen of these genes in primary breast tumors is associated with brain relapse in breast cancer patients. Some of these genes are also associated with metastasis to lung but not to liver, bone or lymph nodes, providing a molecular basis for the long-observed clinical link between brain and lung metastasis. Among the functionally validated brain metastasis genes, the cyclooxygenase COX-2, the EGFR ligand HB-EGF, and the brain-specific α2-6 sialyltransferase ST6GALNAC5 mediate cancer cell passage through the blood-brain barrier. Other brain metastasis genes encode inflammatory factors and brain-specific proteolytic regulators, suggesting a multifaceted program for breast cancer colonization of the brain.
2009-05-06 | GSE12237 | GEO
Project description:Non-small Cell Lung Cancer Brain Metastasis Atlas
| PRJNA926591 | ENA
Project description:Genome wide DNA methylation profiling of brain metastasis from colorectal and lung cancer. The Illumina Infinium MethylationEPIC was used to obtain DNA methylation profiles across approximately 850,000 CpGs in brain metastasis samples. Samples included 1 breast ductal invasive carcinoma, 4 colon adenocarcinoma, 1 melanoma, 1 multiple mieloma, 7 non small cell lung cancer adenocarcinoma, 3 non small cell lung cancer G3, 4 non small cell lung cancer SCC, 1 prostate cancer adenocarcinoma and 1 serous carcinoma.
2023-12-17 | GSE249157 | GEO