Comprehensive circular RNA expression profiling and competitive endogenous RNAs regulatory networks in distal cholangiocarcinoma
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PROVIDER: PRJNA625034 | ENA |
REPOSITORIES: ENA
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Project description:To explore the differentially expressed (DE) circular (circ)RNAs, competing endogenous RNAs networks, and potential biomarkers in distal cholangiocarcinoma (dCCA), using microarray analysis, a comprehensive circRNA expression profiling was constructed with six paired dCCA tumor and adjacent normal samples. A total of 171 DE circRNAs were identified. Three upregulated (hsa_circ_0060144, hsa_circ_0008274, and hsa_circ_0000673) and two downregulated circRNAs (hsa_circ_0139402 and hsa_circ_0001714) were validated with RT-qPCR in 40 dCCA patients. Among them, hsa_circ_0000673 had an idea prognostic efficiency (AUC=0.85, p<0.01) and high level of hsa_circ_0000673 was associated with late tumor stage (p<0.01), poor histodifferentiation (p=0.041), and residual tumor (p=0.044). Gene ontology analysis of the host genes of 171 DE circRNAs showed that “response to nutrient”, “adherens junction”, and “cell adhesion molecule binding” were mainly enriched in terms of biological process, cellular component, and molecular functions respectively. Nine target micro(mi)RNAs of the five DE circRNAs were screened out and enriched in cancer associated pathways. Thereafter, 188 DE mRNAs were predicted as target genes of the nine miRNAs. Finally, protein-protein interaction networks were constructed and 20 hubgenes were identified. This research provided a landscape of DE circRNAs in dCCA, constructed circRNA-miRNA-mRNA regulating networks, and identified hsa_circ_0000673 as a potential biomarker and target for treating dCCA.
2020-12-31 | GSE148561 | GEO
Project description:Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. There is a lack of diagnostic and prognostic biomarkers. An improved understanding of proteomic changes associated with malignancy and identification of potential biomarkers can help improve the survival of patients. A workflow utilizing discovery mass spectrometry and verification by parallel-reaction monitoring was used to analyze surgically resected formalin-fixed paraffin embedded samples from distal cholangiocarcinoma patients and normal bile ducts in order to identify differentially expressed proteins. 20 tumors and 6 controls were successfully analyzed in the discovery experiment and 16 tumors and 9 controls in the PRM analysis. In the discovery experiment a total of 3057 proteins were identified. 87 proteins were found to be differentially expressed between the conditions (q<0.05 and fold change ≥2 or ≤0.5). 31 proteins were upregulated in the distal cholangiocarcinoma samples as compared to controls and 56 downregulated. Bioinformatic analysis revealed an abundance of the differentially expressed proteins to be associated with the tumor reactive stroma. Parallel-reaction monitoring verified 28 proteins as upregulated and 18 as downregulated. In conclusion several proteins without prior association with cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma samples and normal bile ducts. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis.
2020-09-09 | PXD017906 | Pride
Project description:To identify miRNAs differentially expressed in cholangiocarcinoma,3 human cholangiocarcinoma and their corresponding normal bile duct tissues were obtained from 3 patients after operation with postoperative pathological diagnosed perihilar or distal biliary cholangiocarcinoma miRNAs expression in human cholangiocarcinoma/normal bile duct samples was measured after operation.Three independent experiments were performed using different patients for each experiment.
2013-06-10 | E-GEOD-47764 | biostudies-arrayexpress
Project description:To identify miRNAs differentially expressed in cholangiocarcinoma,3 human cholangiocarcinoma and their corresponding normal bile duct tissues were obtained from 3 patients after operation with postoperative pathological diagnosed perihilar or distal biliary cholangiocarcinoma
2013-06-10 | GSE47764 | GEO
Project description:Minimally- invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (CCA) are warranted to enhance early and accurate diagnosis. This study identified tumor tissue secreted proteins, the “secretome”, which was analysed for differential candidate diagnostic plasma proteins. Secretome of tumor and normal tissue was collected directly after resection of the primary tumor from 4 patients with PDAC and distal CCA. The tissue secretome was investigated by label-free LC-MSMS, and database searching identified a total of 5179 proteins. 696 proteins were differentially enriched in tumor secretome compared to normal tissue. Thrombospondin-2 (THBS2) emerged as most promising candidate diagnostic biomarker. Subsequent analysis of THBS2 in plasma samples of patients with PDAC and distal CCA by ELISA showed significantly higher abundance compared to healthy individuals (p<0.001) and resulted in an AUC of 0.844.
2020-05-26 | PXD012480 | Pride
Project description:Distal cholangiocarcinoma (dCCA) is a biliary tract cancer with dismal prognosis and is often preceded by biliary intraepithelial neoplasia (BilIN) as a non-invasive precursor lesion. We found that miR-451a is downregulated in dCCA. Overexpression of mimic-451a in the CCA cell line SNU478 revealed multiple downregulated genes and potential miR-451a candidate targets.
2020-09-01 | GSE147969 | GEO
Project description:Introduction: Accurate diagnosis of distal cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) is a challenge with clinical consequences. Both are lethal malignancies with distinct therapeutic options. This study aimed to identify a circulating microRNA (miRNA) signature to diagnose and discriminate distal CCA from PDAC. Methods: In the discovery phase, microarray profiling of 752 miRNAs was performed on plasma samples of seven patients with distal CCA and seven age- and sex-matched healthy controls. Significant candidate miRNAs were selected for validation based on predefined selection criteria. In the validation phase, these miRNAs were analyzed by RT-qPCR in an independent cohort of healthy controls (n=32), benign periampullary disease (n=20), distal CCA (n=24), and age- sex- and stage-matched PDAC (n=24). Data were normalized to a combination of two reference genes. The optimal diagnostic combination of miRNAs was determined by logistic regression. Sensitivity and specificity were evaluated by ROC curves and AUC values. Results: In the discovery phase, 19 miRNAs were significantly deregulated in patients with distal CCA compared to healthy controls. In the validation phase, 12 candidate miRNAs were selected for validation by RT-qPCR based on pre-defined selection criteria. A two-miRNA panel of downregulated miR-16 and upregulated miR-877 was able accurately distinguish distal CCA from benign disease as well as from PDAC. Conclusion: This is the first study to identify a combined panel of plasma miRNAs which shows promising diagnostic capability to serve as distal CCA signature with the potential to discriminate distal CCA from PDAC.
2019-11-26 | GSE117687 | GEO
Project description:Circular RNAs (circRNAs) play an important role in cholangiocarcinoma (CCA) development; however, the expression and functions of circRNAs in distal CCA (dCCA) remain unknown. Herein, we explored the expression profile of circRNAs in six paired dCCA tumor and adjacent normal tissue samples using microarray. A total of 171 differentially expressed (DE) circRNAs were identified in dCCA tissues. Host genes of DE circRNAs were enriched in the cellular cytoskeleton and adheren junction. Bioinformatics analyses were used to establish a circRNA-microRNA-mRNA network for dCCA. Protein-protein interaction networks were constructed, and five hub genes were associated with the regulation of the cell cycle based on gene set enrichment analyses. Five DE circRNAs were validated with qRT-PCR in 40 pairs of dCCA tissues, and hsa_circ_0000673 showed promising diagnostic performance in distinguishing dCCA from normal tissues (AUC = 0.85, p < 0.01). Overexpression of hsa_circ_0000673 was associated with tumor invasion (p = 0.001), poor differentiation (p = 0.041), and residual tumor (p = 0.044). In vitro experiments indicated that inhibition of hsa_circ_0000673 suppressed the proliferation, migration, and invasion of CCA cells. This research provided a landscape of dysregulated circRNAs in dCCA and identified hsa_circ_0000673 as a potential biomarker and therapeutic target for dCCA.
| S-EPMC7746367 | biostudies-literature
Project description:Biliary intraepithelial neoplasia (BilIN) is a common precursor lesion of distal cholangiocarcinoma (dCCA). However, the sequence leading from a single epithelial layer in normal biliary epithelia to intraepithelial precursor lesions and finally to the invasive tumor is poorly understood. Here, we aimed to elucidate key miRNAs involved in this stepwise process and to identify their possible mRNA target genes in distal cholangiocarcinogenesis. As basis of our study, we conducted Laser Capture Microdissection of FFPE tissue sections of 12 patients with distal cholangiocarcinoma. For each patient, we isolated three matched sample sets, including non-neoplastic biliary epithelia, high grade BilIN (grade 3), and invasive dCCA, thereby representing different stages of distal cholangiocarcinogenesis. This resulted in a total of 36 samples. Total RNA was extracted and the expression of ~800 miRNAs was assessed using the Nanostring® technology. Significantly deregulated miRNAs were validated by quantitative RT-PCR. Target genes were identified using miRWalk2.0 and validated by qRT-PCR and Western blot.
2020-08-07 | GSE140001 | GEO
Project description:Cholangiocarcinoma (CCA) is the second most common type of primary malignancy of the liver. Certain long non-coding RNAs (lncRNAs) have been demonstrated to have key roles in tumor pathogenesis by binding to microRNAs (miRNAs). However, the competing endogenous RNA (ceRNA) network of CCA remains to be fully determined. In the present study, the RNA expression profiles for CCA were downloaded from The Cancer Genome Atlas and further analyzed. A total of 318 differentially expressed (DE) lncRNAs, 87 DE miRNAs and 3,851 DE mRNAs were identified from 36 CCA samples and 9 adjacent non-tumor samples (for lncRNAs and miRNAs, fold change ≥2.5 and P<0.01; for mRNAs, fold change ≥2 and P<0.01). Further bioinformatics analyses were performed and the ceRNA network for CCA was constructed, which included 16 lncRNAs, 55 miRNAs and 373 mRNAs. Survival analysis of all genes in the network revealed that high expression of the mRNAs fucosyltransferase 4 (P<0.005) and huntingtin-interacting protein 1 related (P<0.001) has a positive impact on the overall survival of patients with CAA. Furthermore, the lncRNAs H19 and PVT1, and the miRNAs Homo sapiens (hsa)-miR-16-5p and hsa-miR-424-5p, together with peroxisome proliferator-activated receptors, may also have important roles in the pathogenesis of CCA. The present study provided data to further the understanding of and research into the molecular mechanisms implicated in CCA.
| S-EPMC6796451 | biostudies-literature