scholarly journals A Novel Saliva-Based miRNA Signature for Colorectal Cancer Diagnosis

2019 ◽  
Vol 8 (12) ◽  
pp. 2029 ◽  
Author(s):  
Rapado-González ◽  
Majem ◽  
Álvarez-Castro ◽  
Díaz-Peña ◽  
Abalo ◽  
...  

Salivary microRNAs (miRNAs) are of high interest as diagnostic biomarkers for non-oral cancer. However, little is known about their value for colorectal cancer (CRC) detection. Our study aims to characterize salivary miRNAs in order to identify non-invasive markers for CRC diagnosis. The screening of 754 miRNAs was performed in saliva samples from 14 CRC and 10 healthy controls. The differential expressed miRNAs were validated by RT-qPCR in 51 CRC, 19 adenomas and 37 healthy controls. Receiver operating characteristic (ROC) curves and logistic regression models were performed to analyze the clinical value of these miRNAs. Twenty-two salivary miRNAs were significantly deregulated in CRC patients vs. healthy individuals (P < 0.05) in the discovery phase. From those, five upregulated miRNAs (miR-186-5p, miR-29a-3p, miR-29c-3p, miR-766-3p, and miR-491-5p) were confirmed to be significantly higher in the CRC vs. healthy group (P < 0.05). This five-miRNA signature showed diagnostic value (72% sensitivity, 66.67% specificity, AUC = 0.754) to detect CRC, which was even higher in combination with carcinoembryonic antigen (CEA) levels. Overall, after the first global characterization of salivary miRNAs in CRC, a five-miRNA panel was identified as a promising tool to diagnose this malignancy, representing a novel approach to detect cancer-associated epigenetic alterations using a non-invasive strategy.

1997 ◽  
Vol 43 (12) ◽  
pp. 2339-2344 ◽  
Author(s):  
Volker Keim ◽  
Niels Teich ◽  
Andrea Reich ◽  
Fritz Fiedler ◽  
Joachim Mössner

Abstract We compared the clinical values for diagnosis of acute pancreatitis of two commercial assays for pancreatic elastase: an ELISA procedure with monoclonal antibodies and a RIA technique with polyclonal antibodies. In 14 patients with acute pancreatitis, serum concentrations of elastase determined by ELISA (ELISA-elastase) decreased much faster (half-life 0.4 days) than those of elastase determined by RIA (RIA-elastase) (2.2 days), amylase (0.8 days), or lipase (0.9 days). Serum samples from 253 additional patients with abdominal pain (32 of these with acute pancreatitis) were analyzed. In sera collected up to 48 h after the onset of disease, the ROC curves showed a slightly higher diagnostic value of RIA-elastase. In samples taken later, at a sensitivity of 90% the specificity of RIA-elastase was 95% (ELISA-elastase 40%). We conclude that serum ELISA-elastase is of much lower clinical value than RIA-elastase for diagnosis of acute pancreatitis.


2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Nian-sheng Lai ◽  
Jia-qi Zhang ◽  
Fei-yun Qin ◽  
Bin Sheng ◽  
Xing-gen Fang ◽  
...  

miRNAs are important regulators of translation and have been associated with the pathogenesis of a number of cardiovascular diseases including stroke and may be possible prognostic biomarkers. The purpose of the present study was to determine the expression levels of miRNAs in the sera of subarachnoid haemorrhage (SAH) patients and to evaluate their relationships with the severity and clinical outcome of SAH. Serum samples on day 3 after the onset of SAH were subjected to microarray analysis with Exqion miRCURYTM LNA array and quantitative PCR analysis. Serum samples from SAH patients (n=60) and healthy controls (n=10) were subjected to quantitative PCR analysis. The severities and clinical outcomes of the SAH patients were evaluated with the WFNS grade and the Modified Rankin Scale (mRS). Three miRNAs, miR-502-5p, miR-1297 and miR-4320 were significantly up-regulated in the sera of SAH patients when compared with the healthy controls. The serum miR-502-5p and miR-1297 levels were significantly higher in the patients with severe SAH and a poor outcome than in those with mild SAH and a good outcome (P<0.05). The areas under the receiver operating characteristic (ROC) curves (AUCs) of miR-502-5p, miR-1297 and miR-4320 to distinguish the SAH patients from the healthy controls were 0.958 (P<0.001), 0.950 (P<0.001) and 0.843 (P<0.001) respectively. Taken together, these results indicate that miR-502-5p and miR-1297 are potentially valuable indicators of the diagnosis, severity and prognosis of SAH, and miR-4320 was a potentially valuable indicator of the diagnosis of SAH.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15718-e15718
Author(s):  
Shuichi Mitsunaga ◽  
Shogo Nomura ◽  
Kazuo Hara ◽  
Yukiko Takayama ◽  
Makoto Ueno ◽  
...  

e15718 Background: The diagnostic value of serum microRNAs (miRNA) in a highly sensitive microarray for pancreatobiliary cancer (PBca) has been demonstrated. This study attempted to build and validate a signature comprised of multiple serum miRNA markers for discriminating PBca from healthy controls. Methods: A multicenter prospective study on the diagnostic performance of serum miRNAs was conducted. The patients (pts) with treatment-naïve PBca and healthy participants aged ≥60 years were enrolled. Clinical data and sera were collected. Target population was randomly divided to training or validation cohort with an allocation ratio of 2:1. Twenty-nine serum miRNA markers on the microarray data were analyzed. Using any combinations of the markers, a Fisher’s linear discriminant analysis was performed, and the resulting sensitivity, specificity and AUC of ROC curve to discriminate PBca from healthy controls were calculated for each combination. Marker combinations with a sensitivity/specificity (SN/SP) of ≥80%/90% and high AUC in comparison with AUC of CA19-9 were defined as the diagnostic miRNA signature, which were selected in the training cohort. Next, the signatures were screened out which showed a good reproducibility in the validation cohort. As an independent external cohort, PBca pts and healthy with pooled frozen sera were enrolled and the identified miRNA signatures were further validated. Results: Total of 546 participants (80 healthy and 223 PBca in training set, 40 healthy and 104 PBca in validation set, 49 healthy and 50 PBca in external validation set) were analyzed in this study. Four serum miRNA combinations were identified as the diagnostic miRNA signature. In the training set, four miRNA signatures, consisted of 10 miRNAs, were developed. For the best-performed miRNA signature, the SN/SP and AUC in the validation and external validation cohorts were 84/90% and 0.95 (CA19-9: 73/95% and 0.88) and 84/90% and 0.93 (CA19-9: 80/94% and 0.87), respectively. Conclusions: The diagnostic serum miRNA signatures for PBca were identified in this study.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6679 ◽  
Author(s):  
Mingzhi Xie ◽  
Kezhi Li ◽  
Jilin Li ◽  
Dongcheng Lu ◽  
Bangli Hu

The role of serum serine peptidase inhibitor, Kazal type 4 (SPINK4), in colorectal cancer (CRC) is largely unknown. This study aimed to explore the association and diagnostic value of serum SPINK4 in CRC. A total of 70 preoperative CRC patients, 30 postoperative CRC patients, 30 gastric cancer patients, and 30 healthy controls were enrolled. Using enzyme-linked immunosorbent assays, we found that the serum SPINK4 level was significantly increased in preoperative CRC compared with postoperative CRC patients, gastric cancer patients, and healthy controls (p < 0.05). The serum SPINK4 level was remarkably elevated in colon cancer compared with rectal cancer and was enhanced in the M1 stage compared with the M0 stage (p < 0.05). The area under the receiver operating characteristic curve of serum SPINK4 level in the diagnosis of CRC was 0.9186, with a sensitivity and specificity of 0.886 and 0.900, respectively, and a cut-off value of 2.065. There was no significant difference between high and low expression of serum SPINK4 regarding the overall survival time and disease-free survival (p > 0.05). This study demonstrated that the serum SPINK4 level increased in CRC and was associated with the location and distant metastasis of CRC. It had a high diagnostic value in CRC but was not associated with the survival of CRC patients.


2022 ◽  
Vol 12 ◽  
Author(s):  
Qi Xiao ◽  
Rongyao Hou ◽  
Hong Li ◽  
Shuai Zhang ◽  
Fuzhi Zhang ◽  
...  

Large artery atherosclerotic (LAA) stroke is closely associated with atherosclerosis, characterized by the accumulation of immune cells. Early recognition of LAA stroke is crucial. Circulating exosomal circRNAs profiling represents a promising, noninvasive approach for the detection of LAA stroke. Exosomal circRNA sequencing was used to identify differentially expressed circRNAs between LAA stroke and normal controls. From a further validation stage, the results were validated using RT-qPCR. We then built logistic regression models of exosomal circRNAs based on a large replication stage, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic efficacy. Using exosomal circRNA sequencing, large sample validation, and diagnostic model construction revealed that exosomal circ_0043837 and circ_ 0001801were independent predictive factors for LAA stroke, and had better diagnostic efficacy than plasma circRNAs. In the atherosclerotic group (AS), we developed a nomogram for clinical use that integrated the two-circRNA-based risk factors to predict which patients might have the risk of plaque rupture. Circulating exosomal circRNAs profiling identifies novel predictive biomarkers for the LAA stroke and plaque rupture, with superior diagnostic value than plasma circRNAs. It might facilitate the prevention and better management of this disease.


2018 ◽  
Vol 46 (2) ◽  
pp. 532-545 ◽  
Author(s):  
Yu-Hui Wang ◽  
Jia Ji ◽  
Bi-Cheng Wang ◽  
Hao Chen ◽  
Zhong-Hua Yang ◽  
...  

Background/Aims: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). Methods: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. Results: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. Conclusion: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1542 ◽  
Author(s):  
María Marcuello ◽  
Saray Duran-Sanchon ◽  
Lorena Moreno ◽  
Juan José Lozano ◽  
Luis Bujanda ◽  
...  

Early detection of colorectal cancer (CRC) and its precancerous lesion, advanced adenomas (AA), is critical to improve CRC incidence and prognosis. Circulating microRNAs (miRNAs or miR) are promising non-invasive biomarkers for cancer detection. Our previous results showed that a plasma 6-miRNA signature (miR-15b-5p, miR-18a-5p, miR-29a-3p, miR-335-5p, miR-19a-3p and miR-19b-3p) could distinguish between CRC or AA and healthy individuals (controls). However, its diagnostic performance in serum is unknown. In this exploratory study we aim to evaluate the diagnostic performance of the 6-miRNA signature in serum samples in a cohort of individuals participating in Barcelona’s CRC Screening Programme. We prospectively collected serums from 264 faecal immunochemical test (FIT)-positive participants and total RNA was extracted. Finally, 213 individuals (CRC, 59, AA, 74, controls, 80) were included. MiRNA expression was quantified by real-time RT-qPCR and data analysis was performed by logistic regression. Faecal hemoglobin concentration (f(Hb)) from FIT of the same individuals was also considered. As previously described in plasma, serum from patients with AA or CRC presented significant differences in the 6-miRNA signature compared to controls. Moreover, when combined with f(Hb), the final signature showed high discriminative capacity to distinguish CRC from controls (area under the curve (AUC) = 0.88), and even AA (AUC = 0.81) that otherwise are poorly detected if we only consider f(Hb) (AUC = 0.64). Addition of the serum 6-miRNA signature to quantitative f(Hb) show high accuracy to detect patients with advanced colorectal neoplasia in average-risk individuals. A combination of these two non-invasive methods could be a good strategy to improve diagnostic performances of current CRC screening programmes.


Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 187 ◽  
Author(s):  
Yeying Sun ◽  
Xiaoli Jiang ◽  
Yan Lv ◽  
Xinyue Liang ◽  
Bingrui Zhao ◽  
...  

Heart failure (HF) is a deadly disease that is difficult to accurately diagnose. Circular RNAs (circRNAs) are a novel class of noncoding RNAs that might play important roles in many cardiovascular diseases. However, their role in HF remains unclear. CircRNA microarrays were performed on plasma samples obtained from three patients with HF and three healthy controls. The profiling results were validated by quantitative reverse transcription polymerase chain reaction. The diagnostic value of circRNAs for HF was evaluated by receiver operating characteristic (ROC) curves. The expression profiles indicated that 477 circRNAs were upregulated and 219 were downregulated in the plasma of patients with HF compared with healthy controls. Among the dysregulated circRNAs, hsa_circ_0112085 (p = 0.0032), hsa_circ_0062960 (p = 0.0006), hsa_circ_0053919 (p = 0.0074) and hsa_circ_0014010 (p = 0.025) showed significantly higher expression in patients with HF compared with healthy controls. The area under the ROC curve for hsa_circ_0062960 for HF diagnosis was 0.838 (p < 0.0001). Correlation analysis showed that the expression of hsa_circ_0062960 was highly correlated with B-type natriuretic peptide (BNP) serum levels. Some differential circRNAs were found to be related to platelet activity by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The landscape of circRNA expression profiles may play a role in HF pathogenesis and improve our understanding of platelet function in HF. Moreover, hsa_circ_0062960 has potential as a novel diagnostic biomarker for HF.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wentao He ◽  
Xiaoyi Liu

AbstractWe aimed to provide a laboratory basis for differential diagnosis of COVID-19 and severe fever with thrombocytopenia syndrome (SFTS). Clinical data were collected from 32 COVID-19 patients (2019-nCoV group), 31 SFTS patients (SFTS group) and 30 healthy controls (control group). For each group of hospitalized patients, a retrospective analysis was performed on specific indices, including cytokines, T-lymphocyte subsets, routine blood parameters, C-reactive protein (CRP) and procalcitonin (PCT), and receiver operating characteristic (ROC) curves for the indices revealed the differences among groups. Compared with the 2019-nCoV group, the SFTS group had a significantly and greatly decreased counts of WBC, absolute lymphocyte, PLT and absolute CD4+ T lymphocyte (P < 0.05); the IL-6, TNF-α, D-D and PCT levels of the SFTS group were higher than those of the 2019-nCoV group (P < 0.05). Compared with those of the SFTS group, the CRP and FIB levels of the 2019-nCoV group were greatly increased (P < 0.05). The ROC curves showed that area under the curves (AUCs) for FIB, PLT and TNF-α were greater than 0.85, demonstrating high diagnostic value. At the initial stage of SARS-CoV-2 or SFTS virus infection, PLT, FIB and TNF-α have definitive clinical value for the early and differential diagnosis of these two infections.


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