Retraction: Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.
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SUBMITTER: PLOS Genetics Editors
PROVIDER: S-EPMC9757565 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
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Retraction: Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.
PLoS genetics 20221216 12
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Project description:Brain metastasis (BM) is a major complication of lung adenocarcinoma (LAD). An investigation of the pathogenic mechanisms of BM, as well as the identification of appropriate molecular markers, is necessary. The aim of this study was to determine the expression patterns of microRNAs (miRNAs) in LAD with BM, and to investigate the biological role of these miRNAs during tumorigenesis. miRNA array profiles were used to identify BM-associated miRNAs. These miRNAs were independently validated in 155 LAD patients. Several in vivo and in vitro assays were performed to verify the effects of miRNAs on BM. We identified six miRNAs differentially expressed in patients with BM as compared to patients with BM. Of these, miR-4270 and miR-423-3p were further investigated. miR-4270 and miR-423-3p directly targeted MMP19 and P21, respectively, to influence cell viability, migration, and colony formation in vitro. miR-4270 downregulation and miR-423-3p upregulation was associated with an increased risk of BM in LAD patients. Thus, our results suggested that miR-4270 and miR-423-3p might play an important role in BM pathogenesis in LAD patients, and that these miRNAs might be useful prognostic and clinical treatment targets.
| S-EPMC6374053 | biostudies-literature
Project description:The majority of lung cancer deaths are caused by metastatic disease. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and miRNA dysregulation can contribute to metastatic progression. Here, small RNA sequencing was used to profile the miRNA and piwi-interacting RNA (piRNA) transcriptomes in relation to lung cancer metastasis. RNA-seq was performed using RNA extracted from formalin-fixed paraffin embedded (FFPE) lung adenocarcinomas (LAC) and brain metastases from 8 patients, and LACs from 8 patients without detectable metastatic disease. Impact on miRNA and piRNA transcriptomes was subtle with 9 miRNAs and 8 piRNAs demonstrating differential expression between metastasizing and non-metastasizing LACs. For piRNAs, decreased expression of piR-57125 was the most significantly associated with distant metastasis. Validation by RT-qPCR in a LAC cohort comprising 52 patients confirmed that decreased expression of miR-30a-3p and increased expression of miR-210-3p were significantly associated with the presence of distant metastases. miR-210-3p tumor cell specificity was evaluated by in situ hybridization and its biomarker potential was confirmed by ROC curve analysis (AUC = 0.839). Lastly, agreement between miRNA-seq and RT-qPCR for FFPE-derived RNA was evaluated and a high level of concordance was determined. In conclusion, this study has identified and validated metastasis-related miRNAs in LAC.
| S-EPMC5432317 | biostudies-literature
Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients. 28 brain metastasis samples: 19 from Marc Ladanyi 9 from William L. Gerald
| S-ECPF-GEOD-14108 | biostudies-other
Project description:BackgroundMicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the post-transcriptional level. They participate in a wide variety of biological processes, including apoptosis, proliferation and metastasis. The aberrant expression of miRNAs has been found to play an important role in many cancers.ResultsTo understand the roles of miRNAs in the bone metastasis of lung adenocarcinoma, we constructed two small RNA libraries from blood of lung adenocarcinoma patients with and without bone metastasis. High-throughput sequencing combined with differential expression analysis identified that 7 microRNAs were down-regulated and 21 microRNAs were up-regulated in lung adenocarcinoma with bone metastasis. A total of 797 target genes of the differentially expressed microRNAs were identified using a bioinformatics approach. Functional annotation analysis indicated that a number of pathways might be involved in bone metastasis, survival of the primary origin and metastatic angiogenesis of lung adenocarcinoma. These include the MAPK, Wnt, and NF-kappaB signaling pathways, as well as pathways involving the matrix metalloproteinase, cytoskeletal protein and angiogenesis factors.ConclusionsThis study provides some insights into the molecular mechanisms that underlie lung adenocarcinoma development, thereby aiding the diagnosis and treatment of the disease.
| S-EPMC3620207 | biostudies-literature
Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients. 28 brain metastasis samples: 19 from Marc Ladanyi 9 from William L. Gerald
2010-06-17 | E-GEOD-14108 | biostudies-arrayexpress
Project description:Background: Leptomeningeal metastasis (LM) has frequently been observed in patients with lung adenocarcinoma. So far, its diagnosis and disease course monitoring are still extremely difficult. Moreover, there is no effective treatment regimen for LM due to a lack knowledge on the molecular mechanism of LM. This study aimed to identify LM-related cerebrospinal fluid (CSF) miRNAs, which have potential value for diagnosing and monitoring LM and exploring the molecular mechanism. Methods: CSF miRNAs were screened and verified by microarray analysis and quantitative real-time PCR (qRT-PCR) in LM patients with lung adenocarcinoma and non-LM controls, and the diagnostic performance of candidate miRNAs was evaluated. Then, candidate miRNAs in matched CSF samples from LM patients at diagnosis, after initial therapy, at relapse, and after salvage therapy, were analyzed to assess the relationship between CSF miRNAs and LM disease course. The effect of candidate miRNAs on proliferation, invasion, and migration of lung adenocarcinoma cell lines was assessed. The targeted genes of the candidate miRNA were predicted by TargetScan, miRDB, and miRTarbase online analysis tools. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the functional categories of predicted target genes. Results: CSF miR-7975, miR-7977, and miR-7641 were screened and verified to be statistically significantly up-regulated in LM patients compared to non-LM controls. The three miRNAs, when combined, exhibited optimal diagnostic performance. Longitudinal data of CSF miR-7975 and miR-7977 correlated well with clinical courses of LM. Overexpression of miR-7977 promoted proliferation, migration, and invasion of lung adenocarcinoma cells. Moreover, 385 targeted genes of miR-7977 were predicted and were involved in various pathways related to cancer metastasis. Conclusions: This study offers insights for future research of CSF miRNAs as robust tools for diagnosing and monitoring LM. It also reveals a novel pathway for exploration of underlying mechanisms of LM.
| S-EPMC7152668 | biostudies-literature
Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients.
2010-06-17 | GSE14108 | GEO
Project description:Brain metastasis is a major distant metastasis occurring in patients with advanced breast cancer, and is associated with poor prognosis. MicroRNAs (miRNAs) have a strong influence on various oncological functions and have been reported as potential biomarkers for detecting distant metastasis. Specific biomarkers and unique miRNAs for brain metastasis have yet to be reported. The aim of this study was to identify novel miRNAs in serum, to assist in the diagnosis of brain metastasis in patients with advanced breast cancer. We retrospectively analyzed the medical records of patients with breast cancer and collected clinical data. In addition, we evaluated serum miRNA profiles in patients with breast cancer, with and without brain metastasis, using high-sensitivity microarrays. All patients underwent computed tomography or magnetic resonance imaging brain imaging tests. A total of 51 serum samples from patients with breast cancer and brain metastasis, stored in the National Cancer Center Biobank, were used, and 28 serum samples were obtained from controls without brain metastasis. Two miRNAs, miR-4428 and miR-4480, could significantly distinguish patients with brain metastasis, with area under the receiver operating characteristic curve (AUC) values of 0.779 and 0.781, respectively, while a combination of miR-4428 and progesterone receptor had an AUC value of 0.884. No significant correlations were identified between the expression levels of these two miRNAs in serum and clinical data. We conclude that serum miR-4428 and miR-4480 may be useful as biomarkers for predicting brain metastasis in patients with breast cancer.
| S-EPMC6788729 | biostudies-literature
Project description:Brain metastasis developed in nearly 40% of lung adenocarcinoma (LUAD) patients diagnosed with distant metastasis. There is lack of transcriptomic data of brain lesions from human lung adenocarcinoma patients. As part of the project to understanding the tumor microenvironment in brain metastasis of LUAD patients, we performed bulk RNA analysis on brain metastases from 6 LUAD patients. In order to understand the tumor intrinsic factors that potential shape the tumor microenvironment, we compared these data with bulk RNA sequencing data from 14 early stage and 11 late stage primary LUAD tumor from TCGA database. Pathway expression analysis showed a downregulation of pro-inflammatory signals in brain metastasis and upregulation of DNA synthesis and oxidative phosphorylation pathways related to rapid proliferation in brain lesions.
2019-12-10 | GSE141685 | GEO
Project description:BackgroundLung adenocarcinoma (LUAD), largely remains a primary cause of cancer-related death worldwide. The molecular mechanisms in LUAD metastasis have not been completely uncovered.MethodsIn this study, we identified differentially expressed genes (DEGs), miRNAs (DEMs) and lncRNAs (DELs) underlying metastasis of LUAD from The Cancer Genome Atlas database. Intersection mRNAs were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and co-expression network analysis. In addition, survival analyses of intersection mRNAs were conducted. Finally, intersection mRNAs, miRNAs and lncRNAs were subjected to construct miRNA-mRNA-lncRNA network.ResultsA total of 1015 DEGs, 54 DEMs and 22 DELs were identified in LUAD metastasis and non-metastasis samples. GO and KEGG pathway analysis had proven that the functions of intersection mRNAs were closely related with many important processes in cancer pathogenesis. Among the co-expression interactions network, 22 genes in the co-expression network were over the degree 20. These genes imply that they have connections with many other gene nodes. In addition, 14 target genes (ARHGAP11A, ASPM, HELLS, PRC1, TMPO, ARHGAP30, CD52, IL16, IRF8, P2RY13, PRKCB, PTPRC, SASH3 and TRAF3IP3) were found to be associated with survival in patients with LUAD significantly (log-rank P < 0.05). Two lncRNAs (LOC96610 and ADAM6) acting as ceRNAs were identified based on the miRNA-mRNA-lncRNA network.ConclusionsTaken together, the results may provide a novel perspective to develop a multiple gene diagnostic tool for LUAD prognosis, which might also provide potential biomarkers or therapeutic targets for LUAD.
| S-EPMC6307237 | biostudies-literature