Identification of Circulating MiR-25 as a Potential Biomarker for Pancreatic Cancer Diagnosis

Background: The aim of this study was to identify novel microRNAs for potential use in the diagnosis of pancreatic cancer (PaC). Methods: A total of 1063 serum samples from 303 patients with PaC were collected, and the expression level of miR-25 was measured using quantitative real-time PCR (qRT-PCR). Results: We found that miR-25 had significant diagnostic value for the differential diagnosis of PaC in normal controls with an AUC (the area under the ROC curve) of 0.915 (95% CI: 0.893-0.937) that was significantly higher compared with an AUC of 0.725 for serum tumor marker carcinoembryonic antigen (CEA) and an AUC of 0.844 for CA19-9. Conclusions: These data suggest that serum miR-25 has strong potential as a novel biomarker for the early detection of PaC.

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Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

Biomolecules ◽

10.3390/biom10071083 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1083

Author(s):

Aleksandra Filimoniuk ◽

Agnieszka Blachnio-Zabielska ◽

Monika Imierska ◽

Dariusz Marek Lebensztejn ◽

Urszula Daniluk

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

High Performance ◽

Area Under The Curve ◽

Study Groups ◽

Diagnostic Value ◽

Serum Samples ◽

Specificity And Sensitivity ◽

Potential Biomarker ◽

Inflammatory Bowel

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.

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Diagnostic value of macrophage inhibitory cytokine 1 as a novel prognostic biomarkers for early gastric cancer screening

10.21203/rs.3.rs-17962/v1 ◽

2020 ◽

Author(s):

Xin Ge ◽

Xiaolei Zhang ◽

Yanling Ma ◽

Shaohua Chen ◽

Zhaowu Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Cancer Diagnosis ◽

Early Stage ◽

Precancerous Lesions ◽

Diagnostic Value ◽

Low Grade ◽

Serum Samples ◽

Early Screening ◽

Roc Curve Analysis

Abstract BACKGROUND Early diagnosis is very important to improve the survival rate of patients with gastric cancer, especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of gastric cancer. In this study, we explored whether MIC-1 can improve the detection rate of early gastric cancer.METHODS We screened 8,257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4 and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4 and PG1/PG2, and its role in early gastric cancer diagnosis and the assessment of the risk of precancerous lesions have also been studied.RESULTS Based on endoscopic and histopathological findings, 55 participants had gastric cancer, 566 participants had low-grade neoplasia, 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in gastric cancer serum samples as compared to controls (p<0.001). The sensitivity of serum MIC-1 for gastric cancer diagnosis was much higher than that of CA-199 (49.1% vs. 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4 and PG1/PG2 in distinguishing early-stage gastric cancer (AUC: 72.9% vs. 69.5%, 67.5%, 44.0% respectively).CONCLUSIONS Serum MIC-1 is significantly elevated in most patients with early gastric cancer. MIC-1 can serve as a novel diagnostic marker of early gastric cancer and value the risk of gastric cancer.

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SOX9 stands for a bio-marker for prostate cancer detection

10.21203/rs.3.rs-53227/v1 ◽

2020 ◽

Author(s):

Hao Zi ◽

Wen-Lin Tao ◽

Lei Gao ◽

Zhao-Hua Yu ◽

Xiao-Dong Bai ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Detection ◽

Roc Curve ◽

Operating Characteristic ◽

Diagnostic Value ◽

Quantitative Real Time Pcr ◽

Optimal Cutoff ◽

Qrt Pcr ◽

Incidence And Mortality ◽

The Relationship

Abstract Background Prostate cancer is one of common cancers around the world, and in our country the incidence and mortality of PCa are both increasing. More and more reports have revealed that SOX9 is involved in various human cancers. In this study, we aimed to explore the relationship between SOX9 expression and diagnostic value of PCa patients. Methods In this study, quantitative real-time PCR (qRT-PCR) was performed to determine the expression of SOX9 of the 131 PCa patients and 74 healthy volunteers. And receiver operating characteristic (ROC) curve was used to determine the diagnostic value of SOX9 for PCa patients. Results The results of qRT-PCR showed that the expression of serum SOX9 in PCa patients was higher than that in healthy controls (P < 0.05). And the expression of SOX9 was significantly associated with PSA (P = 0.001), differentiation (P = 0.000), and lymph node metastasis (P = 0.000). Besides, the area under the ROC curve (AUC) was 0.966 with the sensitivity of 93.2% and specificity of 87.8% respectively. The optimal cutoff value of SOX9 was 2.34. Conclusions Our results found that SOX9 is a novel oncogene for PCa, and may be a novel and effective biomarker for the diagnosis of patients with PCa.

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Diagnostic Value of Plasma miR-181b, miR-196a, and miR-210 Combination in Pancreatic Cancer

Gastroenterology Research and Practice ◽

10.1155/2020/6073150 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Gongpan Liu ◽

Cunhua Shao ◽

Anyun Li ◽

Xiaobin Zhang ◽

Xingjun Guo ◽

...

Keyword(s):

Pancreatic Cancer ◽

Vascular Invasion ◽

Operating Characteristic ◽

Clinical Stage ◽

Diagnostic Value ◽

Carbohydrate Antigen ◽

Plasma Samples ◽

Healthy Individuals ◽

Qrt Pcr ◽

Node Metastasis

Purpose. This study was aimed at investigating the roles of plasma miR-181b, miR-196a, and miR-210 in the diagnosis of pancreatic cancer (PC). Methods. Plasma samples were isolated from 40 patients with PC and 40 healthy individuals, respectively. The expression of miR-181b, miR-196a, and miR-210 was detected by qRT-PCR. The level of carbohydrate antigen 199 (CA199) was measured by an electrochemiluminescence (ECL) assay. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of miR-181b, miR-196a, miR-210, CA199, and their combinations in PC. Results. The expression of plasma miR-181b, miR-196a, and miR-210 was significantly upregulated in PC patients. The plasma level of CA199 was also significantly increased in PC patients. The expression of miR-181b, miR-196a, and miR-210 was closely associated with lymph node metastasis, clinical stage, and vascular invasion but not correlated with age, gender, and tumor size. miR-181b, miR-196a, and miR-210 have lower AUC than CA199 in the diagnosis of PC. miR-181b+miR-210 and miR-196a+miR-210 also have lower AUC than CA199. It is worth noting that miR-181b+miR-196a+miR-210 has a higher AUC than CA199 in the diagnosis of PC. Conclusion. The combination of plasma miR-181b, miR-196a, and miR-210 had a good diagnostic value for PC.

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CircRNA circ_0075796 is downregulated in breast cancer and suppresses cell proliferation, migration and invasion

10.21203/rs.3.rs-1074679/v1 ◽

2021 ◽

Author(s):

Yao Xu ◽

Ya-Wen Wang ◽

Xu Chen ◽

Can Liu ◽

Yan-Duo Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Bioinformatics Analysis ◽

Diagnostic Value ◽

Migration And Invasion ◽

Normal Tissues ◽

Qrt Pcr ◽

Cancer Tissues ◽

Normal Controls

Abstract Background Emerging evidence shows that circular RNAs (circRNAs) play crucial parts in tumorigenesis and progression. In this work, the expression, clinical significance, function and potential mechanism of circ_0075796 in breast cancer were explored. Methods The expression of circ_0075796 in 189 pairs of breast cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay, methyl thiazolyl tetrazolium (MTT) assay and colony formation assay were conducted for cell proliferation. Transwell assay and wound healing assay were used for cell migration and invasion. Flow cytometry analysis was adopted for cell cycle and cell apoptosis. The cellular localization of circ_0075796 was determined by fluorescence in situ hybridization (FISH). The circ_0075796/miR-452-3p/SAMD5 axis was screened out by bioinformatics analysis and verified by qRT-PCR. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m6A) modification levels of circ_0075796. QRT-PCR was used to detect the expression of RNA binding protein Quaking (QKI) in breast cancer tissues and adjacent normal tissues. Results circ_0075796 was downregulated in breast cancer tissues compared with adjacent normal tissues. In addition, circ_0075796 showed satisfactory diagnostic value to discriminate breast cancer and normal controls. Downregulated circ_0075796 expression was correlated with lymph node metastasis, HER2 expression, larger tumor size, high Ki-67 expression, advanced histological grade, aggressive molecular subtypes and advanced clinical stages. Overexpression of circ_0075796 inhibited cell proliferation, migration and invasion in vitro. FISH showed that circ_0075796 was localized in the cytoplasm and nucleus of breast cancer cells. Bioinformatics analysis and qRT-PCR revealed the potential circ_0075796/miR-452-3p/SAMD5 axis. Moreover, circ_0075796 showed lower m6A modification levels in breast cancer tissues compared to adjacent normal tissues. QKI was predicted to contain binding sites of circ_0075796 and was downregulated in breast cancer tissues compared to adjacent normal controls. Conclusions circ_0075796 was downregulated in breast cancer compared to normal controls, and showed potential diagnostic value for breast cancer. Downregulation of circ_0075796 was correlated with aggressive clinical features of breast cancer and overexpression of circ_0075796 inhibited the progression of breast cancer in vitro, indicating that circ_0075796 may be related to tumorigenesis and development of breast cancer.

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Upregulation of long non-coding RNA LOC284454 may serve as a new serum biomarker for head and neck cancers

10.21203/rs.3.rs-17647/v3 ◽

2020 ◽

Author(s):

Chunmei Fan ◽

Jinpeng Wang ◽

Yanyan Tang ◽

Shanshan Zhang ◽

Fang Xiong ◽

...

Keyword(s):

Early Diagnosis ◽

Head And Neck ◽

Diagnostic Value ◽

Head And Neck Cancers ◽

Serum Biomarker ◽

Operating Characteristics ◽

Clinical Value ◽

Serum Samples ◽

Non Coding Rna ◽

Normal Controls

Abstract Background: Identification of effective diagnostic and prognostic biomarkers of cancer is necessary for improving precision medicine. Long non-coding RNAs (lncRNAs) play an important regulatory role in tumor initiation and progression. The lncRNA LOC284454 is distinctly expressed in various head and neck cancers (HNCs), as demonstrated by our previous bioinformatics analysis. However, the expression levels and functions of LOC284454 in cancer are still unclear.Methods: We investigated the dysregulation of lncRNAs in HNCs using the GEO database and found that LOC284454 was highly expressed in HNCs. Serum samples from 212 patients with HNCs and 121 normal controls were included in this biomarker study. We measured the expression of LOC284454 in the sera of HNC patients and normal controls using RT-qPCR. Receiver operating characteristics (ROC) analysis is an important statistical method that is widely used in clinical diagnosis and disease screening. ROC was used to analyze the clinical value of LOC284454 in the early diagnosis of HNCs.Results: LOC284454 was significantly upregulated in the sera of patients with nasopharyngeal carcinoma, oral cancer, and thyroid cancer. LOC284454 upregulation had good clinical diagnostic value in these cancers, as evaluated by area under the ROC curve values of 0.931, 0.698, and 0.834, respectively.Conclusions:LOC284454 may be a valuable serum biomarker for HNCs facilitating the early diagnosis of malignant cancers. Further studies are needed to elucidate the mechanisms underlying the involvement of LOC284454 in HNCs. This study provides the first evidence that LOC284454 may be a serum biomarker for HNCs.

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Serum MicroRNA Expression Profile as a Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer

Clinical Chemistry ◽

10.1373/clinchem.2011.172767 ◽

2012 ◽

Vol 58 (3) ◽

pp. 610-618 ◽

Cited By ~ 245

Author(s):

Rui Liu ◽

Xi Chen ◽

Yiqi Du ◽

Weiyan Yao ◽

Lin Shen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Expression Profile ◽

High Sensitivity ◽

Diagnostic Value ◽

Serum Samples ◽

Double Blind ◽

Serum Mirna ◽

Diagnosis And Prognosis ◽

Serum Microrna ◽

Specificity And Sensitivity

Abstract BACKGROUND Detection of pancreatic cancer (PaC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers. We sought to identify a PaC-specific serum microRNA (miRNA) expression profile and test its specificity and sensitivity as a biomarker in the diagnosis and prognosis of PaC. METHODS We obtained serum samples from 197 PaC cases and 158 age- and sex-matched cancer-free controls. We screened the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled serum samples followed by RT-qPCR validation of a large number of samples arranged in multiple stages. We used risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. To assess the serum miRNA–based biomarker accuracy in predicting PaC, we performed additional double-blind testing in 77 PaC cases and 52 controls and diagnostic classification in 55 cases with clinically suspected PaC. RESULTS After the selection and validation process, 7 miRNAs displayed significantly different expression levels in PaC compared with controls. This 7 miRNA–based biomarker had high sensitivity and specificity for distinguishing various stages of PaC from cancer-free controls and also accurately discriminated PaC patients from chronic pancreatitis (CP) patients. Among the 7 miRNAs, miR-21 levels in serum were significantly associated with overall PaC survival. The diagnostic accuracy rate of the 7-miRNA profile was 83.6% in correctly classifying 55 cases with clinically suspected PaC. CONCLUSIONS These data demonstrate that the 7 miRNA–based biomarker can serve as a novel noninvasive approach for PaC diagnosis and prognosis.

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Early Second-Trimester Serum MicroRNAs as Potential Biomarker for Nondiabetic Macrosomia

BioMed Research International ◽

10.1155/2014/394125 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Lingmin Hu ◽

Jing Han ◽

Fangxiu Zheng ◽

Hongxia Ma ◽

Jiaping Chen ◽

...

Keyword(s):

Characteristic Curve ◽

External Validation ◽

Serum Samples ◽

Qrt Pcr ◽

Discovery Phase ◽

Rapid Economic Growth ◽

Potential Biomarker ◽

Noninvasive Biomarker ◽

Pooled Samples ◽

Serum Micrornas

Background. Macrosomia has become a worldwide problem with the rapid economic growth in the past few years. However, the detailed mechanism of how the macrosomia happened remains unknown. Growing evidence indicates that miRNAs are involved in maintaining metabolic homeostasis. We hypothesized that serum miRNAs are potential biomarkers for macrosomia.Methods. We performed miRNAs profiling using TLDA chips in the discovery phase in two pooled samples from 30 cases and 30 controls, respectively. Individual qRT-PCR was conducted for the discovery phase samples. To confirm the results, we detected the miRNAs which were differentially expressed in the microarray assays and individual qRT-PCR in external validation phase with another 30 cases and 30 controls.Results. In the discovery stage, miR-194 and miR-376a expression levels were significantly different between macrosomia group and controls (P=0.048for miR-194 andP=0.018for miR-376a, resp.). Further evaluation of the two miRNAs on a total of 120 serum samples showed that the miR-376a remains significantly lower in macrosomia (P=0.032). Receiver operating characteristic curve analyses showed that the area under curve for miR-376a was 67.8% (sensitivity = 96.7% and specificity = 40.0%).Conclusions. Serum miR-376a may serve as a potential noninvasive biomarker in detecting macrosomia.

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Serum Exosomal MicroRNA, miR-10b-5p, as a Potential Diagnostic Biomarker for Early-Stage Hepatocellular Carcinoma

Journal of Clinical Medicine ◽

10.3390/jcm9010281 ◽

2020 ◽

Vol 9 (1) ◽

pp. 281 ◽

Cited By ~ 13

Author(s):

Hyo Cho ◽

Jung Eun ◽

Geum Baek ◽

Chul Seo ◽

Hye Ahn ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Validation Cohort ◽

Early Stage ◽

Area Under The Curve ◽

Disease Free Survival ◽

Pcr Analysis ◽

Serum Samples ◽

Qrt Pcr ◽

Normal Hepatocyte ◽

Potential Biomarker

Exosomal microRNAs (exo-miRs) have been promising cancer biomarkers. MiRs in hepatocellular carcinoma (HCC) cell-derived exosomes (HEX) were analyzed to identify reliable serum biomarkers for HCC. To detect overexpressed miRs in HEX, extracted exosomal small RNAs from human HCC cell lines and normal hepatocytes were sequenced and analyzed. Clinical significance of the overexpressed miRs in HEX was evaluated using quantitative real-time PCR (qRT-PCR) on serum samples of a validation cohort consisting of 28 healthy individuals, 60 with chronic liver disease, and 90 with HCC. We found 49 significantly overexpressed miRs in HEX compared to a normal hepatocyte. Among them, miR-10b-5p, miR-18a-5p, miR-215-5p, and miR-940 were overexpressed in HCC tissues and also associated with prognosis of HCC in the analysis of a public omics database. qRT-PCR analysis of the four serum exo-miRs in the validation cohort revealed serum exo-miR-10b-5p as a promising biomarker for early-stage HCC with 0.934 area under the curve (AUC) (sensitivity, 90.7%; specificity, 75.0%; cutoff value, 1.8-fold). Overexpression of serum exo-miR-215-5p was found to be significantly associated with poor disease-free survival in patients with HCC. Serum exo-miR-10b-5p is a potential biomarker for early-stage HCC, while serum exo-miR-215-5p can be used as prognostic biomarker for HCC.

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Experimental Validation of a Potential Circulating microRNA Panel for Non-Invasive Pancreatic Cancer Diagnosis

10.21203/rs.3.rs-936432/v1 ◽

2021 ◽

Author(s):

Ali Seyed Salehi ◽

Negar Parsa ◽

Farnaz Roshan-Farzad ◽

Ali Behmanesh ◽

Mohadeseh Fathi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Differential Expression Analysis ◽

External Validation ◽

Diagnostic Value ◽

Ductal Adenocarcinoma ◽

Circulating Microrna ◽

Plasma Samples ◽

Serum Samples ◽

Non Invasive ◽

Testing Stage

Abstract MicroRNA (miRNA) expression dysregulations in pancreatic ductal adenocarcinoma (PDAC) have been studied widely for their diagnostic and prognostic utility. By the use of Bioinformatics-based methods, in our previous study, we identified some potential miRNA panels for diagnosis of Pancreatic cancer patients from non-cancerous controls (the screening stage). In this report, we used 142 plasma samples from people with and without pancreatic cancer (PC) to conduct RT-qPCR differential expression analysis to assess the strength of the first previously proposed diagnostic panel (consisting of miR-125a-3p, miR-4530 and miR-92a-2-5p). For this aim the research was divided into two phases: testing, and external validation. A total of 92 PC plasma samples and normal controls (NCs) were evaluated in the testing stage to determine the ability of the considered miRNAs to discriminate cancer from non-cancer samples as a panel. Furthermore, in the external validation phase, a group of 25 PC serum samples vs. 25 NCs was employed to validate the diagnostic value of the panel. As the result, we identified significant up-regulation for all the three considered miRNAs in the serum of PC patients. After that, a three-miRNA panel in serum was developed. For the testing, validating and combined stages, the area under the receiver operating characteristic curves (AUC) for the panel were 0.850, 0.910 and 0.86 respectively, indicating that it had a higher diagnostic value than individual miRNAs. Therefore, we detected a promising three-miRNA panel in the plasma for non-invasive PC diagnosis (miR-125a-3p, miR-4530 and miR-92a-2-5p).

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