scholarly journals Identification of Circulating Serum miRNAs as Novel Biomarkers in Pancreatic Cancer Using a Penalized Algorithm

2021 ◽  
Vol 22 (3) ◽  
pp. 1007
Author(s):  
Jaehoon Lee ◽  
Hee Seung Lee ◽  
Soo Been Park ◽  
Chanyang Kim ◽  
Kahee Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
High Sensitivity ◽  
Training Model ◽  
Carbohydrate Antigen ◽  
Support Vector ◽  
Serum Samples ◽  
Absolute Deviation ◽  
Non Invasive ◽  
Diagnosis Model

Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers and build a model for PC diagnosis. For the training model, blood serum samples from 63 PC patients and 63 control subjects were used. We selected 39 miRNA markers using a smoothly clipped absolute deviation-based penalized support vector machine and built a PC diagnosis model. From the double cross-validation, the average test AUC was 0.98. We validated the diagnosis model using independent samples from 25 PC patients and 81 patients with intrahepatic cholangiocarcinoma (ICC) and compared the results with those obtained from the diagnosis using carbohydrate antigen 19-9. For the markers miR-155-5p, miR-4284, miR-346, miR-7145-5p, miR-5100, miR-661, miR-22-3p, miR-4486, let-7b-5p, and miR-4703-5p, we conducted quantitative reverse transcription PCR using samples from 17 independent PC patients, 8 ICC patients, and 8 healthy individuals. Differential expression was observed in samples from PC patients. The diagnosis model based on the identified markers showed high sensitivity and specificity for PC detection and is potentially useful for early PC diagnosis.

scholarly journals Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imteyaz Ahmad Khan ◽  
Safoora Rashid ◽  
Nidhi Singh ◽  
Sumaira Rashid ◽  
Vishwajeet Singh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Next Generation ◽  
Serum Samples ◽  
Tissue Samples ◽  
Non Invasive ◽  
Specific Symptoms ◽  
Generation Sequencing

AbstractEarly-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

scholarly journals Time–frequency analysis of serum with proton nuclear magnetic resonance for diagnosis of pancreatic cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Asahi Sato ◽  
Toshihiko Masui ◽  
Akitada Yogo ◽  
Takashi Ito ◽  
Keiko Hirakawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Carbohydrate Antigen ◽  
Serum Markers ◽  
Proton Nuclear Magnetic Resonance ◽  
Serum Samples ◽  
Time Frequency ◽  
H Nmr ◽  
Free Induction ◽  
Short Time ◽  
Long Term Survivors

AbstractAlthough serum markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) have been widely used in screening for pancreatic cancer (PC), their sensitivity and specificity are unsatisfactory. Recently, a novel tool of analyzing serum using the short-time Fourier transform (STFT) of free induction decays (FIDs) obtained by 1H-NMR has been introduced. We for the first time evaluated the utility of this technology as a diagnostic tool for PC. Serum was obtained from PC patients before starting any treatments. Samples taken from individuals with benign diseases or donors for liver transplantation were obtained as controls. Serum samples from both groups underwent 1H-NMR and STFT of FIDs. STFT data were analyzed by partial least squares discriminant analysis (PLS-DA) to clarify whether differences were apparent between groups. As a result, PLS-DA score plots indicated that STFT of FIDs enabled effective classification of groups with and without PC. Additionally, in a subgroup of PC, long-term survivors (≥ 2 years) could be discriminated from short-term survivors (< 2 years), regardless of pathologic stage or CEA or CA19-9 levels. In conclusion, STFT of FIDs obtained from 1H-NMR have a potential to be a diagnostic and prognostic tool of PC.

Can IL-2R Alpha be a Valuable Marker along with Ca 19–9 in the Diagnosis of Chronic Pancreatitis and Pancreatic Cancer?

2004 ◽  
Vol 19 (3) ◽  
pp. 196-202
Author(s):  
B. Kayhan ◽  
B. Kayhan ◽  
M. Akdoğ;an
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Interleukin 2 ◽  
Carbohydrate Antigen ◽  
Control Group ◽  
Serum Samples ◽  
Cancer Group ◽  
Abdominal Symptoms ◽  
Significant Difference ◽  
Inflammatory Processes

Background Pancreatic cancer is characterized initially by non-specific abdominal symptoms followed by rapid tumor progression. Although chronic pancreatitis is a benign disorder, it can be one of the causative factors of pancreatic cancer. The level of the tumor marker carbohydrate antigen 19–9 (CA 19–9) in pancreatic cancer does not correlate with the stage of the neoplasm. Soluble interleukin 2 receptor (sIL-2R) is a cytokine that shows increased levels during some inflammatory processes and malignant disorders. Aim Our aim in this study was to investigate whether sIL-2Rα levels can be used in association with CA 19–9 in the early diagnosis of pancreatic cancer and chronic pancreatitis. Patients Serum samples were obtained from the blood of 21 pancreatic cancer patients without distant metastasis who were deemed inoperable, 16 chronic pancreatitis patients and 20 normal volunteers. Results We did not find any significant differences in CA 19–9 levels between normal controls and patients with chronic pancreatitis. There was a significant difference in the levels between the control group and the pancreatic cancer group (p=0.003) and between patients with chronic pancreatitis and those with pancreatic cancer (p=0.004). Although there was no significant difference in sIL-2Rα levels between the control group and the patient groups, we found a slight correlation between sIL-2Rα and CA 19–9 levels in the pancreatic cancer group (p=0.003, r=0.623) and a more marked correlation in the chronic pancreatitis group (p<0.01, r=0.751). Conclusion According to our results, sIL-2Rα alone is not a good candidate marker in the diagnosis of pancreatic cancer; it can, however, be used in association with CA 19–9 for this purpose.

scholarly journals Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gulfem D. Guler ◽  
Yuhong Ning ◽  
Chin-Jen Ku ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Cell Free Dna ◽  
Early Stage Disease ◽  
Non Invasive ◽  
Cancer Pathogenesis ◽  
Free Dna ◽  
Stage Disease ◽  
Circulating Cell Free Dna

Abstract Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.

scholarly journals Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

2018 ◽  
Author(s):  
Francois Collin ◽  
Yuhong Ning ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
Aaron Scott ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Training Data ◽  
Ductal Adenocarcinoma ◽  
Data Sets ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Pancreatic Cancers ◽  
Free Dna ◽  
Circulating Cell Free Dna

AbstractPancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial by enabling surgical resection or earlier application of therapeutic regimens. We investigated the detection of pancreatic ductal adenocarcinoma (PDAC) in a non-invasive manner by interrogating changes in 5-hydroxymethylation cytosine status (5hmC) of circulating cell free DNA in the plasma of a PDAC cohort (n=51) in comparison with a non-cancer cohort (n=41). We found that 5hmC sites are enriched in a disease and stage specific manner in exons, 3’UTRs and transcription termination sites. Our data show that 5hmC density is reduced in promoters and histone H3K4me3-associated sites with progressive disease suggesting increased transcriptional activity. 5hmC density is differentially represented in thousands of genes, and a stringently filtered set of the most significant genes points to biology related to pancreas (GATA4, GATA6, PROX1, ONECUT1) and/or cancer development (YAP1, TEAD1, PROX1, ONECUT1, ONECUT2, IGF1 and IGF2). Regularized regression models were built using 5hmC densities in statistically filtered genes or a comprehensive set of highly variable 5hmC counts in genes and performed with an AUC = 0.94-0.96 on training data. We were able to test the ability to classify PDAC and non-cancer samples with the Elastic net and Lasso models on two external pancreatic cancer 5hmC data sets and found validation performance to be AUC = 0.74-0.97. The findings suggest that 5hmC changes enable classification of PDAC patients with high fidelity and are worthy of further investigation on larger cohorts of patient samples.

scholarly journals Meta-analysis of the diagnostic performance of circulating microRNAs for pancreatic cancer

2020 ◽  
Author(s):  
Cheng Peng ◽  
Zhiqiang Li ◽  
Lihua Huang ◽  
Wenzhe Gao ◽  
Jiale Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Diagnostic Accuracy ◽  
Diagnostic Performance ◽  
Early Stage ◽  
Meta Analysis ◽  
Carbohydrate Antigen ◽  
Cochrane Library ◽  
Circulating Mirnas ◽  
China National Knowledge Infrastructure ◽  
Circulating Micrornas

Abstract Background: Pancreatic cancer (PC) is characterized by high malignancy and a poor prognosis. The detection of circulating microRNAs (miRNAs) is a liquid biopsy diagnostic approaches. Numerous studies have suggested that some differentially expressed miRNAs may be promising diagnostic markers for PC, but the results have varied among studies. The present study was performed to summarize the diagnostic accuracy of circulating miRNAs, carbohydrate antigen 19-9 (CA19-9), and the combination of miRNAs and CA19-9.Methods: A literature search of online databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang was conducted. Relative data were extracted from eligible included studies, and a meta-analysis was performed.Results: A total of 46 studies involving 4,326 PC patients and 4,277 non-PC controls were included. The pooled sensitivity (SEN), specificity (SPE) and AUC of the circulating miRNAs for differentiating PC patients from non-PC controls were 0.79 (0.77-0.81), 0.77 (0.75-0.79), and 0.85 (0.81-0.87), respectively. For CA19-9, the SEN, SPE and AUC were 0.78 (0.75-0.80), 0.90 (0.85-0.94) and 0.85 (0.82-0.88), respectively. The combination of miRNAs and CA19-9 greatly improved the SEN, SPE and AUC to 0.84 (0.80-0.87), 0.91 (0.89-0.93) and 0.94 (0.92-0.96), respectively. Moreover, circulating miRNAs also yielded an acceptable diagnostic accuracy for early-stage PC with a SEN of 0.79 (0.76-0.82), a SPE of 0.74 (0.68-0.79) and an AUC of 0.81 (0.77-0.84).Conclusions: Circulating miRNAs exhibited satisfactory diagnostic performance for PC and even early-stage PC. The combination of circulating miRNAs and the traditional marker CA19-9 can further improve the diagnostic accuracy, providing a novel strategy for PC diagnosis.

scholarly journals Exploring the extracellular transcriptome in seminal plasma for non-invasive prostate cancer diagnosis

2021 ◽  
Author(s):  
Eva Hulstaert ◽  
Annelien Morlion ◽  
Justine Nuytens ◽  
Giovanni Ponti ◽  
Monia Maccaferri ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Seminal Plasma ◽  
Messenger Rna ◽  
Early Stage ◽  
High Sensitivity ◽  
Fusion Transcript ◽  
Prostate Hyperplasia ◽  
Non Invasive ◽  
Cancer Group ◽  
Cancer Pathogenesis

A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA (mRNA) profile of seminal plasma has not been interrogated for its biomarker potential in the context of prostate cancer. Here, we investigate the mRNA transcriptome in seminal plasma samples obtained from prostate cancer patients (n=25), patients with benign prostate hyperplasia (n=26) and individuals without prostatic disease (n=6). Seminal plasma harbors a complex mRNA repertoire that reflects prostate as its tissue of origin. The endogenous RNA content is higher in the prostate cancer samples compared to the control samples. Prostate cancer antigen 3 (PCA3), a long non-coding RNA with prostate cancer-specific overexpression, and ATP-binding cassette transporter 1 (ABCA1), known to be involved in the prostate cancer pathogenesis, were more abundant in the prostate cancer group. In addition, twelve high confidence fusion transcripts could be detected in prostate cancer samples, including the bona-fide prostate cancer fusion transcript TMPRSS2-ERG. Our findings provide proof-of-principle that the extracellular transcriptome of seminal plasma can reveal information of an underlying prostate cancer.

scholarly journals O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2469 ◽  
Author(s):  
Takahiro Yokose ◽  
Yasuaki Kabe ◽  
Atsushi Matsuda ◽  
Minoru Kitago ◽  
Sachiko Matsuda ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Vesicles ◽  
Early Stage ◽  
Absolute Quantification ◽  
Serum Marker ◽  
Carbohydrate Antigen ◽  
Liquid Biopsies ◽  
Lectin Microarray ◽  
High Area ◽  
Quantitative Analyses

Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

scholarly journals Raman spectroscopy as a non-invasive diagnostic technique for endometriosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ugur Parlatan ◽  
Medine Tuna Inanc ◽  
Bahar Yuksel Ozgor ◽  
Engin Oral ◽  
Ercan Bastu ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Diagnostic Technique ◽  
Principal Component ◽  
Classification Model ◽  
Support Vector ◽  
Serum Samples ◽  
K Nearest Neighbors ◽  
Non Invasive ◽  
Unseen Data ◽  
Invasive Method

AbstractEndometriosis is a condition in which the endometrium, the layer of tissue that usually covers the inside of the uterus, grows outside the uterus. One of its severe effects is sub-fertility. The exact reason for endometriosis is still unknown and under investigation. Tracking the symptoms is not sufficient for diagnosing the disease. A successful diagnosis can only be made using laparoscopy. During the disease, the amount of some molecules (i.e., proteins, antigens) changes in the blood. Raman spectroscopy provides information about biochemicals without using dyes or external labels. In this study, Raman spectroscopy is used as a non-invasive diagnostic method for endometriosis. The Raman spectra of 94 serum samples acquired from 49 patients and 45 healthy individuals were compared for this study. Principal Component Analysis (PCA), k- Nearest Neighbors (kNN), and Support Vector Machines (SVM) were used in the analysis. According to the results (using 80 measurements for training and 14 measurements for the test set), it was found that kNN-weighted gave the best classification model with sensitivity and specificity values of 80.5% and 89.7%, respectively. Testing the model with unseen data yielded a sensitivity value of 100% and a specificity value of 100%. To the best of our knowledge, this is the first study in which Raman spectroscopy was used in combination with PCA and classification algorithms as a non-invasive method applied on blood sera for the diagnosis of endometriosis.

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