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A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients

ABSTRACT: A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients

PROVIDER: PRJNA817569 | ENA |

REPOSITORIES: ENA

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A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients.

Project description:To date, the 5-year overall survival of early-stage non-small cell lung cancer (NSCLC) is still unsatisfactory at 59.8%. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on a double interconnection between cancer cells and the surrounding tumor microenvironment; hence, circulating molecules may represent promising markers of cancer recurrence. Here, we performed in-depth analysis of circolome-derived markers, including Exo-miRnome and peptidome in 67 radically resected NSCLCs, to identify a prognostic score. The miRnome profile selected exo-miR130a-3p as the most overexpressed in patients with relapse. Peptidome analysis identified 4 progressively more degraded forms of fibrinopeptide A (fpA) in progressing patients. Notably, the combination of exo-miR130a-3p and the greatest fpA (2-16) built a score where high-risk patients had 24 months of disease-free survival. Moreover, in vitro transfections showed that higher levels of exo-miR-130a-3p lead to a deregulation of some pathways involved in metastasis, in angiogenesis, such as in coagulation which could be linked to the FpA reduction. In conclusion, the identified risk score integrating circulating markers can help clinicians predict early-stage NSCLC patients who are more likely to relapse after initial surgery.

2022-03-16 | MSV000089072 | MassIVE

A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients [miRNA]

Project description:To date, the 5-year overall survival of early stage non-small cell lung cancer (NSCLC) is still unsatisfactory at 59.8%. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on a double interconnection between cancer cells and the surrounding tumor microenvironment, and circulating molecules may represent promising markers of cancer recurrence. Here, we performed in-depth analysis of circolome-derived markers, including Exo-miRnome and peptidome in 67 radically resected NSCLCs, to identify a prognostic score. The miRnome profile selected exo-miR130a-3p as the most overexpressed in patients with relapse. Peptidome analysis identified 4 fibrinopeptide A (fpA), which were depleted in progressing patients. Notably, the combination of exo-miR130a-3p and the greatest fpA (2-16) built a score where high-risk patients had 24 months of disease-free survival. Moreover, in vitro transfections showed that higher levels of exo-miR-130a-3p lead to a deregulation of some pathways involved in metastasis, in angiogenesis, such as in coagulation. In conclusion, the identified risk score integrating circulating markers can help clinicians predict early-stage NSCLC patients who are more likely to relapse after initial surgery.

2022-05-01 | GSE198958 | GEO

A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients [Nanostring]

Project description:To date, the 5-year overall survival of early stage non-small cell lung cancer (NSCLC) is still unsatisfactory at 59.8%. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on a double interconnection between cancer cells and the surrounding tumor microenvironment, and circulating molecules may represent promising markers of cancer recurrence. Here, we performed in-depth analysis of circolome-derived markers, including Exo-miRnome and peptidome in 67 radically resected NSCLCs, to identify a prognostic score. The miRnome profile selected exo-miR130a-3p as the most overexpressed in patients with relapse. Peptidome analysis identified 4 fibrinopeptide A (fpA), which were depleted in progressing patients. Notably, the combination of exo-miR130a-3p and the greatest fpA (2-16) built a score where high-risk patients had 24 months of disease-free survival. Moreover, in vitro transfections showed that higher levels of exo-miR-130a-3p lead to a deregulation of some pathways involved in metastasis, in angiogenesis, such as in coagulation which could be linked to the FpA reduction. In conclusion, the identified risk score integrating circulating markers can help clinicians predict early-stage NSCLC patients who are more likely to relapse after initial surgery.

2022-05-01 | GSE198957 | GEO

A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients [Nanostring]

Project description:A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients [Nanostring]

| PRJNA817571 | ENA

A circulating risk score, based on combination of exo-miR130a-3p and fibrinopeptide A, as predictive biomarker of relapse in early stage non-small cell lung cancer patients [miRNA]

| PRJNA817572 | ENA

miRNAs in adipose tissue derived exosomes (Exo-AT) and adipose stem cells derived exosomes (Exo-ADSCs)

Project description:The emerging evidences support that exosome cargo miRNAs function as important regulators in cell differentiation. Therefore, in order to figure out the mechanism that Exo-AT mediated adipogenesis, we profiled miRNAs in Exo-AT using high-throughput sequencing (miRNA-seq). After trimming low-quality reads, contaminants, adaptors, and reads smaller than 15 nt, the remaining reads were mapped to merged pre-miRNA data bases. To identify the conserved miRNAs in Exo exosomes, miRNAs were aligned to miRBase v21. 148 and 154 types of known miRNAs in Exo-ADSCs and Exo-AT, respectively, were identified in the two replicates. Among these miRNAs, 103 miRNAs were simultaneously detected in both Exo-ADSCs and Exo-AT. Compared to Exo-ADSCs, 45 conserved miRNAs were enriched (expressed ≥ 2 folds, FDR<0.05) in Exo-AT. KEGG Pathway analysis was performed for the targets of the most 20 enriched miRNAs in Exo-AT (compared with Exo-ADSCs) to determine their potential function. Data showed that pathways that regulate adipogenesis such as Wnt signaling pathway, Insulin signaling pathway, MAPK signaling pathway, TGF-ß signaling pathway were enriched significantly for targets of Exo-AT miRNAs. Furthermore, 14 of 45 enriched miRNAs in Exo-AT (31.11%, such as miR-30a-5p, miR-148a-3p) were reported to participate in regulation of adipogenesis while 8 miRNAs (17.78%, such as miR-93-5p, miR-150-3p) that negatively control osteoblastic differentiation of MSC have been described.

2018-12-01 | GSE92313 | GEO

miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signaling in human colorectal adenocarcinoma cells

Project description:Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks.

2017-03-29 | MSV000080762 | MassIVE

miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signaling in human colorectal adenocarcinoma cells

2016-08-12 | PXD002172 | Pride

BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats

Project description:BMSC-derived exosomes from ovariectomized rats (OVX-Exo) and sham-operated rats (Sham-Exo) were co-cultured with bone marrow-derived macrophages to study their effects on osteoclast differentiation. Next-generation sequencing was utilized to identify the differentially expressed miRNAs (DE-miRNAs) in OVX-Exo and Sham-Exo, while target genes were analyzed using bioinformatics. The regulatory effects of miR-27a-3p and miR-196b-5p on osteogenic differentiation of BMSCs and osteoclast differentiation were verified by gain-of-function and loss-of-function analyses.Osteoclast differentiation was significantly enhanced in the OVX-Exo treatment group compared to the Sham-Exo group. Twenty DE-miRNAs were identified in OVX-Exo and Sham-Exo, among which miR-27a-3p and miR-196b-5p promoted the expressions of osteogenic genes in BMSCs. In contrast, knockdown of miR-27a-3p and miR-196b-5p increased the expressions of osteoclastic genes in osteoclasts. These 20 DE-miRNAs were found to target 11435 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these target genes were involved in several biological processes and osteoporosis-related signaling pathways.

2022-07-07 | GSE197085 | GEO

A Circulating Risk Score, Based on Combined Expression of Exo-miR-130a-3p and Fibrinopeptide A, as Predictive Biomarker of Relapse in Resectable Non-Small Cell Lung Cancer Patients.

Project description:To date, the 5-year overall survival rate of 60% for early-stage non-small cell lung cancer (NSCLC) is still unsatisfactory. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on an interconnection between cancer cells and the surrounding tumor microenvironment; hence, circulating molecules may represent promising markers of cancer recurrence. In order to identify a prognostic score, we performed in-depth high-throughput analyses of plasma circulating markers, including exosomal microRNAs (Exo-miR) and peptides, in 67 radically resected NSCLCs. The miRnome profile selected the Exo-miR-130a-3p as the most overexpressed in relapsed patients. Peptidome analysis identified four progressively more degraded forms of fibrinopeptide A (FpA), which were depleted in progressing patients. Notably, stepwise Cox regression analysis selected Exo-miR-130a-3p and the greatest FpA (2-16) to build a score predictive of recurrence, where high-risk patients had 18 months of median disease-free survival. Moreover, in vitro transfections showed that higher levels of miR-130a-3p lead to a deregulation of pathways involved in metastasis and angiogenesis, including the coagulation process and metalloprotease increase which might be linked to FpA reduction. In conclusion, by integrating circulating markers, the identified risk score may help clinicians predict early-stage NSCLC patients who are more likely to relapse after primary surgery.

| S-EPMC9317031 | biostudies-literature

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