Combination of four serum exosomal miRNAs as novel diagnostic biomarkers for early-stage gastric cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE130654 | GEO | 2020/02/21
REPOSITORIES: GEO
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Project description:Objective: The expression pattern of exosomal miRNAs derived from parathyroid tumor is still unknown. In the present work, we aimed to examine the differences on microRNA (miRNA) expression, present in serum exosomes, by comparing parathyroid carcinoma (PC) and parathyroid adenoma (PA). Methods: MiRNA expression profile of serum exosomes, derived from 4 PC patients and 4 PA patients, were analyzed by next-generation sequencing technology. The differential expressions of target miRNAs were further verified in both serum exosomes and tissues of PC/PA patients by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Lastly, receiver operating characteristic (ROC) curves were plotted to investigate the efficiency of target exosomal miRNAs in distinguishing PC patients from PA controls. Results: Multiple differentially expressed miRNAs of serum exosomes were screened out by sequencing. Based on this screening, hsa-miR-146b-5p (p=0.0846), hsa-miR-27a-5p (p=0.0412), hsa-miR-93-5p (p=0.73), hsa-miR-381-3p (p=0.1239) and hsa-miR-134-5p (p=0.0694) were up-regulated in the serum exosomes of PC patients. These results were validated by qPCR, where the trend on differential miRNA expression was consistent with the sequencing results. Specifically, the expression of exosomal hsa-miR-27a-5p was able to clearly distinguish PC patients from PA controls, and related analysis indicated that the area under the ROC curve was 0.8594 (p=0.0157). Conclusion: Here we present, for the first time, the miRNA expression profile of serum exosomes derived from PC patients. Based on this result, we presently suggest that the exosomal hsa-miR-27a-5p may serve as a putative tumor marker for preoperative identification of PC and PA subjects.
2020-11-13 | GSE161339 | GEO
Project description:Circulating microRNAs (miRNAs) in serum may serve as promising diagnostic biomarkers for patients with gastric cancer (GC). Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel, we identified 58 differentially expressed miRNAs from 3 GC pool samples and 1 normal control (NC) pool in the initial screening phase. Identified miRNAs were further validated in the training (49 GC VS. 47 NCs) and validation phases (154 GC VS. 120 NCs) using qRT-PCR. Consequently, six serum miRNAs (miR-10b-5p, miR-132-3p, miR-185-5p, miR-195-5p, miR-20a-3p and miR-296-5p) were significantly overexpressed in GC compared with NCs. The areas under the receiver operating characteristic (ROC) curve of the six-miRNA panel were 0.764 and 0.702 for the training and validation phases, respectively. In conclusion, we identified a six-miRNA panel in serum for the detection of GC.
2016-08-31 | GSE86226 | GEO
Project description:Purpose: Gastric cancer (GC) is one of the most common causes of cancer deaths worldwide; however, reliable and non-invasive screening methods for GC are not established. Therefore, we conducted this study to develop a biomarker for GC detection, consisting of urinary microRNAs (miRNAs). Experimental Design: We matched 306 participants by age and sex (153 pairs consisting of patients with GC and healthy controls [HCs]), then randomly divided them across three groups: (1) the discovery cohort (4 pairs); (2) the training cohort (95 pairs); (3) the validation cohort (54 pairs). Moreover, 64 participants (32 pairs) with serum samples were also enrolled in the serum cohort. Result: There were 22 urinary miRNAs with significantly aberrant expressions between the two groups in the discovery cohort. Upon multivariate analysis of the training cohort, urinary expression levels of miR-6807-5p and miR-6856-5p were significantly independent biomarkers for diagnosis of GC, in addition to Helicobacter pylori (H. pylori) status. A diagnostic panel that combined the aberrant miRNAs and H. pylori status distinguished between HC and GC samples with an area under the curve (AUC) = 0.736. In the validation cohort, urinary miR-6807-5p and miR-6856-5p showed significantly higher expression levels in the GC group, and the combination biomarker panel of miR-6807-5p, miR-6856-5p, and H. pylori status also showed excellent performance (AUC = 0.885). In addition, serum levels of miR-6807-5p and miR-6856-5p were significantly higher in the GC group. Conclusion: This novel biomarker panel enables early and non-invasive detection of GC.
2019-12-22 | GSE128720 | GEO
Project description:Aims: Differential expression profiles of microRNAs (miRNAs) are associated with autoimmune diseases. This study sought to elucidate the plasma exosomal miRNA expression profiles of patients with rheumatoid arthritis (RA) and their potential clinical significance. Methods: In the screening phase, small RNA sequencing was performed to characterize dysregulated exosome-derived miRNAs in the plasma samples from six RA patients and six healthy controls. In the independent validation phase, the candidate plasma exosomal miRNAs were verified in 40 RA patients and 32 healthy controls using quantitative real-time PCR. The association of miRNA levels with clinical characteristics in RA patients was tested. The value of these miRNAs in diagnosing RA was assessed with the receiver operating characteristic curve. Results: Totally 177 and 129 miRNAs were upregulated and downregulated, respectively in RA patients versus healthy controls in the screening phase. There were 10 candidate plasma exosomal miRNAs selected for the next identification. Compared with the healthy controls, eight plasma exosomal miRNAs (let-7a-5p, let-7b-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-128-3p, and miR-25-3p) were significantly elevated in RA patients, but miR-144-3p and miR-15a-5p expression exhibited no significant changes. The let-7a-5p and miR-25-3p levels were associated with rheumatoid factor-positive phenotype in RA patients. For the eight miRNAs, the area under the receiver operating characteristic curve (AUC) ranged from 0.641 to 0.843, and their combination had a high diagnostic accuracy for RA (AUC = 0.916). Conclusions: Our study illustrates that novel exosomal miRNAs in the plasma may represent potential noninvasive biomarkers for RA.
2023-09-24 | GSE218599 | GEO
Project description:From serum samples of non-dialyzed and dialyzed patients with ADPKD and healthy control total RNA was isolated and miRNA expression was evaluated. Circulating microRNAs (miRNA) are important intercellular communication compounds. We investigated the influence of ADPKD (autosomal dominant polycystic kidney disease) and hemodialysis on the profile of serum miRNAs. We found 37 significant circulating miRNA that differ between ADPKD patients (dialyzed and non-dialyzed) and healthy controls. Bioinformatic analysis revealed strongest connections between those miRNAs and KEGG pathway: MicroRNAs in cancer. We selected 3 miRNAs with highest and 3 with lowest fold change in comparison of dialyzed and non-dialyzed patients and compared their expression in paired pre-/post-dialysis samples. All up-regulated miRNAs (miR-532-3p, miR-320b, miR-144-5p) were not significantly altered by hemodialysis. From down-regulated miRNAs miR-27a-3p was shown to be significantly lower after dialysis in both total and exosomal fraction. MiR-20a-5p was down-regulated after dialysis only in the exosomal fraction whereas miR-16-5p was unaltered by hemodialysis. MiR-16-5p was selected as the best circulating biomarker of ADPKD with miR-22-3p, let-7i-5p and miR-24-3p as following best ones. Circulating representatives of miR-17 family (new drug target of ADPKD (Hajarnis et al. 2017)) sharing the same seed region (miR-20a-5p, miR-93-5p and miR-106a-5p) showed significantly lowered expressed in sera of dialyzed patients vs non-dialyzed ones and their exosomal fraction dropped after hemodialysis. We concluded that serum miRNA among ADPKD patients differ substantially depending on the stage of CKD. These alterations show possible links with cancer. The exosomal fraction of miRNA was more affected by dialysis than total fraction of miRNAs suggesting their dynamically changing functional role.
2018-06-30 | GSE101811 | GEO
Project description:Despite the recent interest in plasma microRNA (miRNA) biomarkers in acute ischemic stroke patients, there is limited knowledge about the miRNAs directly related to stroke itself due to the multiple complications in patients, which has hindered the research progress of biomarkers and therapeutic targets of ischemic stroke. Therefore, in this study, we compared the differentially expressed miRNA profiles in the plasma of three rhesus monkeys pre- and post-cerebral ischemia. After cerebral ischemia, RFAM sequence category revealed increased ribosomic RNA (rRNA) and decreased transfer RNAs (tRNAs) in plasma. Of the 2049 miRNAs detected after cerebral ischemia, 36 were upregulated, and 76 were downregulated (fold change ≥2.0, P <0.05). For example, Mml-miR-191-5p, miR-421, miR-409-5p, and let-7g-5p were found to be significantly overexpressed, whereas mml-miR-128a-5p_R-2, miR-431_R-1, and let-7g-3p_1ss22CT were significantly downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these differentially expressed miRNAs were implicated in the regulation of ubiquitin-mediated proteolysis and signaling pathways in cancer, glioma, chronic myeloid leukemia, and chemokine signaling. miRNA clustering analysis showed that mml-let-7g-5p and let-7g-3p_1ss22CT, which share three target genes (RB1CC1, GNG5, and CXCR4), belong to one cluster, were altered in opposite directions following ischemia. These data suggest that circulating mml-let-7g may serve as a therapeutic target for ischemic stroke.
2021-08-27 | GSE182429 | GEO
Project description:Sertoli cells (SCs), the only somatic constituent of the testicular seminiferous epithelium, are vital to spermatogenesis. We previously found that vitamin C (ascorbic acid, AA) can reprogram the transcriptome, and promote the proliferation and reproductive function of pig immature SCs (iSCs). However, the global change of microRNAs (miRNA) expression and its effect on pig iSCs as induced by vitamin C treatment is still unknown. Here, we performed small RNA sequencing on pig iSCs after 250μM AA2P (L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate) treatment for 36h. Total number of detected miRNAs ranged from 326-335 known, and 400-570 novel miRNAs. Of the top ten highly expressed miRNAs, we found that 8 were common (miR-21-5p, let-7i-5p, miR-30a-5p, let-7f-5p, let-7g, miR-100, miR-10a-5p and miR-30d), which were predicted to target mRNAs involved in cell development and differentiation. We identified 78 differentially expressed (DE) miRNAs (|log2 foldchange|≥1; Padj.<0.05), including 7 known and 71 novel miRNAs. We further selected 13 highly and stably expressed DE miRNAs (4 up-regulated: miR-184, novel-miR-610, novel-miR-316 and novel-miR-1274; 9 down-regulated: miR-222, miR-221-5p, miR-221-3p, miR-210, miR-146b, miR-146a-5p, novel-miR-182, novel-miR-1088 and novel-miR-1016), and performed integrated analysis on the miRNA-mRNA regulatory network. DE mRNAs negatively targeted by these 13 DE miRNAs were enriched in multiple GO and KEGG signaling pathways (e.g. pyruvate and steroid metabolic processes, developmental process in reproduction, response to oxidative stress, Glycolysis/Gluconeogenesis and HIF-1). We validated 8 DE miRNAs and their 12 DE mRNA targets, with expression patterns consistent with (mi)RNA-seq results. Taken together, our findings demonstrate that vitamin C could induce the global change of miRNAs, which possibly regulate cell proliferation, energy metabolism and male reproduction as induced by vitamin C treatment on pig iSCs.
2024-04-10 | GSE171850 | GEO
Project description:We aimed at extending the repertoire of high-quality miRNA normalizers for reverse transcription-quantitative PCR (RT-qPCR) of human plasma with special emphasis on the extremely guanine-cytosine-rich portion of the miRNome. For high-throughput selection of stable candidates, microarray technology was preferred over small-RNA sequencing (sRNA-seq) since the latter underrepresented miRNAs with a guanine-cytosine (GC) content of at least 75% (p = 0.0002, n = 2). miRNA abundances measured on the microarray were ranked for consistency and uniformity using nine normalization approaches. The eleven most stable sequences included miRNAs of moderate, but also extreme GC content (45%–65%: miR-320d, miR-425-5p, miR-185-5p, miR-486-5p; 80%–95%: miR-1915-3p, miR-3656-5p, miR-3665-5p, miR-3960-5p, miR-4488-5p, miR-4497 and miR-4787-5p). In contrast, the seven extremely GC-rich miRNAs were not found in the two plasma miRNomes screened by sRNA-seq. Stem-loop RT-qPCR was employed for stability verification in 32 plasma samples of healthy male Caucasians (age range: 18–55 years). In general, inter-individual variance of miRNA abundance was low or very low as indicated by coefficient of variation (CV) values of 0.6%–8.2%. miR-3665 and miR-1915-3p outperformed in this analysis (CVs: 0.6 and 2.4%, respectively). The eight most stable sequences included four extremely GC-rich miRNAs (miR-1915-3p, miR-3665, miR-4787-5p and miR-4497). The best-performing duo normalization factor (NF) for the condition of human plasma, miR-320d and miR-4787-5p, also included a GC-extreme miRNA. In summary, the identification of extremely guanine-cytosine-rich plasma normalizers will help to increase accuracy of PCR-based miRNA quantification, thus raise the potential that miRNAs become markers for psychological stress reactions or early and precise diagnosis of clinical phenotypes. The novel miRNAs might also be useful for orthologous contexts considering their conservation in related animal genomes.
2022-07-25 | GSE209568 | GEO
Project description:In this study we compared the miRNA expression profile of 217 CLL cases versus various normal B cell subpopulations in the attempt of finding the normal cell subset most similar to CLL cells and gain information on possible miRNA deregulations. Our analyses indicated that CLL cells exhibited a miRNA expression pattern close to memory and marginal zone-like B cells. Conversely, tonsil GC and CD19+ peripheral blood B cells appeared only distantly related to CLL. Memory and marginal zone B cells were used as reference to identify differentially expressed miRNAs in CLL, which included miR-193b, miR-33b*, miR-365, miR-181b and miR-196a/b among the down-regulated and miR-23a/b, miR-26a, miR-130a, miR-532 (5p and 3p) among the up-regulated miRNAs. We also investigated differences of miRNA expression related to the IGHV somatic mutation status and to deletions at 13q, 11q and 17p or trisomy 12. Little differences were detected between unmutated (UM) versus mutated (M) CLLs, although miR-29c, miR-29c* and miR-146b were strongly down-modulated in the UM-CLL subgroup. Each of the cytogenetic classes of CLL was characterized by uniquely abnormally expressed miRNAs. Deletion at 13q displayed a reduced expression of miR-16, more evident if the deletion was biallelic. Deletion of 17p was characterized by the strong reduction of miR-34a expression and up-regulation of miR-96. Deletion at 11q was characterized by the up-regulation of miR-338-3p and miR-769-5p. Trisomy 12 was characterized by a strong down-regulation of miR-483-5p.
2014-03-01 | E-MTAB-1454 | biostudies-arrayexpress
Project description:We tested the hypothesis that a panel of placental mammal-specific miRNAs and their targets play important to establish receptivity to implantation and their dysregulated expression may be a feature in women with early pregnancy loss. Relative expression levels of miR-340-5p, −542-3p, and −671-5p all increased following treatment of Ishikawa cells with progesterone (10 μg/ml) for 24 hrs (p < 0.05). RNA sequencing of these P4-treated cells identified co-ordinate changes to 6,367 transcripts of which 1713 were predicted targets of miR-340-5p, 670 of miR-542-3p, and 618 of miR-671-5p. Quantitative proteomic analysis of Ishikawa cells transfected with mimic or inhibitor (48 hrs: n=3 biological replicates) for each of the P4-regulated miRNAs was carried out to identify targets of these miRNAs. Excluding off target effects, mir-340-5p mimic altered 1,369 proteins while inhibition changed expression of 376 proteins (p < 0.05) of which, 72 were common to both treatments. A total of 280 proteins were identified between predicted (mirDB) and confirmed (in vitro) targets. In total, 171 proteins predicted to be targets by mirDB were altered in vitro by treatment with miR-340-5p mimic or inhibitor and were also altered by treatment of endometrial epithelial cells with P4. In vitro targets of miR-542-3p identified 1,378 proteins altered by mimic while inhibition altered 975 a core of 200 proteins were changed by both. 100 protein targets were predicted and only 46 proteins were P4 regulated. miR-671-mimic altered 1,252 proteins with inhibition changing 492 proteins of which 97 were common to both, 95 were miDB predicted targets and 46 were also P4-regulated. All miRNAs were detected in endometrial biopsies taken from patients during the luteal phase of their cycle, irrespective of prior or future pregnancy outcomes Expression of mir-340-5p showed an overall increase in patients who had previously suffered a miscarriage and had a subsequent miscarriage, as compared to those who had infertility or previous miscarriage and subsequently went on to have a life birth outcome. The regulation of these miRNAs and their protein targets regulate the function of transport and secretion, and adhesion of the endometrial epithelia required for successful implantation in humans. Dysfunction of these miRNAs (and therefore the targets they regulate) may contribute to endometrial-derived recurrent pregnancy loss in women.
2023-05-10 | PXD036109 | Pride