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.

Development of extracellular vesicles-based classifier for detection of early-stage bladder, ovarian, and pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3048-3048
Author(s):  
Juan Pablo Hinestrosa ◽  
Razelle Kurzrock ◽  
Jean Lewis ◽  
Nick Schork ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Confidence Interval ◽  
Extracellular Vesicles ◽  
Metastatic Disease ◽  
Cancer Detection ◽  
Early Stage ◽  
Expression Patterns ◽  
Stepwise Logistic Regression ◽  
Liquid Biopsies ◽  
Cancer Early Detection

3048 Background: Many cancers are lethal because they present with metastatic disease. Because localized/resectable tumors produce vague symptoms, diagnosis is delayed. In pancreatic cancer, only ̃10% of patients survive five years, and it will soon become the second leading cause of cancer-related deaths in the USA. For patients with metastatic disease, the 2- and 5-year survival is < 10% and ̃3%, respectively. For the few patients with local disease, 5-year survival is ̃40%. Many other cancers have comparable differences between early- and late-stage disease. It is apparent a diagnostic assay for early-stage cancers would transform the field by minimizing the need for aggressive surgeries and other harsh interventions, and by its potential to increase survival. Identifying cancer-specific aberrations in blood-based “liquid” biopsies offers a prospect for a non-invasive cancer detection tool. In the bloodstream, there are extracellular vesicles (EVs) with cargoes including membrane and cytosolic proteins, as well as RNA and lipids derived from their parent cells. Methods: We used an alternating current electrokinetics (ACE) microarray to isolate EVs from the plasma of stage I and II bladder (N = 48), ovarian (N = 42), and pancreatic cancer patients (N = 44), and healthy volunteers (N = 110). EVs were analyzed using multiplex protein immunoassays for 54 cancer-related proteins. EV protein expression patterns were analyzed using stepwise logistic regression followed by a split between training and test sets (67%/33% respectively). This process enabled biomarker selection and generation of a classifier to discriminate between cancer and healthy donors. Results: The EV protein-based classifier had an overall area under curve (AUC) of 0.95 with a sensitivity of 71.2% (69.4% – 73.0%, at 95% confidence interval) at > 99% specificity. The classifier’s performance for the pancreatic cancer cohort was very strong, with overall sensitivity of 95.7% (94.6% – 96.9%, at 95% confidence interval) at > 99% specificity. Conclusions: EV-associated proteins may enable early cancer detection where surgical resection is most likely to improve outcomes. The classifier’s performance for the initial three cancers studied showed encouraging results. Future efforts will include examining additional cancer types and evaluating the classifier performance using samples from donors with related benign conditions with the aim of a pan-cancer early detection assay.

A Serum Marker for Early Pancreatic Cancer with a Possible Link to Diabetes

2021 ◽  
Author(s):  
Hoonsik Nam ◽  
Sunmi Kang ◽  
Min Seok Park ◽  
Suyeon Kang ◽  
Han Sun Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Normal Cell ◽  
Diagnostic Performance ◽  
Early Stage ◽  
Serum Marker ◽  
Diabetic Patients ◽  
Diagnostic Biomarker ◽  
Diabetic Status ◽  
Validation Set

Abstract Background Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well-established. Methods Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic subjects) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9. Results Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic AUC of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). Conclusion Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.

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 Exosomal Non Coding RNA in LIQUID Biopsies as a Promising Biomarker for Colorectal Cancer

2020 ◽  
Vol 21 (4) ◽  
pp. 1398 ◽  
Author(s):  
Amro Baassiri ◽  
Farah Nassar ◽  
Deborah Mukherji ◽  
Ali Shamseddine ◽  
Rihab Nasr ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sensitivity And Specificity ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Noncoding Rnas ◽  
Predictive Biomarkers ◽  
Carbohydrate Antigen ◽  
Combination Regimen ◽  
Liquid Biopsies ◽  
Diagnostic Potential

Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific and could serve as predictive biomarkers for the most common chemotherapeutic drug and combination regimen in CRC, which are 5-FU and FOLFOX, respectively. Therefore, in this review, we focus on the role of these exosomal noncoding RNAs as diagnostic, prognostic, and predictive biomarkers. In addition, we discuss the advantages and challenges of exosomes as a liquid biopsy target.

Correlation between tumor markers in pre and post treatment of pancreatic cancer patients

2021 ◽  
Vol 25 (1) ◽  
pp. 70-74
Author(s):  
N. Sivakumar ◽  
R. Arivazhagan ◽  
B. Prabasheela
Keyword(s):  
Pancreatic Cancer ◽  
Tumour Marker ◽  
Serum Marker ◽  
Carbohydrate Antigen ◽  
Tumour Markers ◽  
Post Treatment ◽  
Treatment Groups ◽  
Serum Tumour Marker ◽  
Before And After ◽  
Serum Tumour

One of the main causes of death in India is pancreas cancer. Various blood tumour indicators such as 19-9 carbohydrate antigen (CA19-9), antigen125 carbohydrate (CA125), antigen carcinoembryogenic (CEA) and alphaetoprotein (AFP) imbalance are observed in therapy for cancer. In disease predictions, thorough monitoring of the change in serum tumour markers was highly essential. The present investigation was thus conducted to examine serum marker tumour profiles before and after therapy of individuals with pancreatic cancer. The study comprised 400 individuals from both sexes suffering from pancreatic carcinogenic malignancy. In the pre and post-treatment of patients we detected serum tumour markers. In post-treatment groups, serum tumour marker levels were lower than before the individuals were treated. However, using pairs of samples t-testing at pfleg.0.05 these changes were statistically significant. Marker alterations in the serum tumour have shown risk for individuals. These alterations therefore enable the cancer individuals to predict and monitor properly.

Combination of CA19-9 and Blood Free-Circulating Methylated RUNX3 May Be Useful to Diagnose Stage I Pancreatic Cancer

Oncology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Yuko Fujimoto ◽  
Yutaka Suehiro ◽  
Seiji Kaino ◽  
Shigeyuki Suenaga ◽  
Takanori Tsuyama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Digital Pcr ◽  
Pancreatic Disease ◽  
Carbohydrate Antigen ◽  
Screening Strategy ◽  
Response To Therapy ◽  
Stage I ◽  
Bisulfite Treatment ◽  
Sample Amount

<b><i>Background:</i></b> Although serum carbohydrate antigen 19-9 (CA19-9) is widely used as a useful biomarker of pancreatic cancer for monitoring the response to therapy, it is not recommended for screening of early pancreatic cancer because of its limited sensitivity for small tumors. Thus, it is critical to discover novel serum biomarkers to complement CA19-9 in order to improve sensitivity. Although methylated runt-related transcription factor 3 (<i>RUNX3</i>) is a biomarker of pancreatic cancer, its detection by conventional bisulfite-based methylation assays from a small serum sample amount is very difficult. Therefore, we developed a new methylation assay, the combined restriction digital PCR (CORD) assay, that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. <b><i>Objectives:</i></b> We evaluated the sensitivity and specificity of serum DNA testing of methylated <i>RUNX3</i> by the CORD assay in combination with and without CA19-9 for the detection of pancreatic cancer in 55 patients with pancreatic cancer, 12 patients with benign pancreatic disease, and 80 healthy individuals. <b><i>Results:</i></b> The CORD assay of methylated <i>RUNX3</i> had a sensitivity of 50.9% (28/55) and specificity of 93.5% (86/92). Combination of the CORD assay of methylated <i>RUNX3</i> and CA19-9 resulted in a sensitivity of 85.5% (47/55) and specificity of 93.5% (86/92) for all stages of pancreatic cancer and a sensitivity of 77.8% (7/9) for stage I pancreatic cancer. <b><i>Conclusions:</i></b> ombination of the CORD assay and CA19-9 may provide an alternative screening strategy for detecting early-stage pancreatic cancer.

scholarly journals Endosialin (TEM1) as a Diagnostic, Progression, and Prognostic Serum Marker for Patients With Colorectal Cancer—A Preliminary Study

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090335
Author(s):  
Łukasz Pietrzyk ◽  
Paulina Wdowiak
Keyword(s):  
Colorectal Cancer ◽  
Serum Concentration ◽  
Early Stage ◽  
Serum Marker ◽  
Carbohydrate Antigen ◽  
Stage I ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Serum Samples ◽  
The Mean

Colorectal cancer (CRC) is one of the most common cancers worldwide usually diagnosed in the advanced stage. In this study, the serum concentration of tumor endothelial marker 1 (TEM1) was measured and correlated with clinicopathological features to evaluate whether TEM1 might serve as a biomarker for early CRC diagnosis, progression, and prognosis. The concentration of TEM1 was measured in the serum samples of 45 patients with CRC and 35 healthy individuals using enzyme-linked immunosorbent assay test. The mean serum concentration of TEM1 was significantly higher in the patients with CRC compared to the healthy individuals (1.31 ± 0.16 vs 0.92 ± 0.90 ng/mL; P < .001). The mean concentration of TEM1 significantly increased in the patients having CRC with early stage (stage I + II) compared to noncancer control individuals (stage I + II vs control 1.21 ± 0.13 ng/mL: 0.92 ± 0.90 ng/mL; P < .001). The TEM1 concentration in blood serum also showed a significant association with the development of T stages ( P < .001), N stages ( P < .001), and M stages ( P = .006). The TEM1 sensitivity and specificity in CRC detection are higher than routinely used blood markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [Ca 19-9]). Patients with high TEM1 concentration (≥1.055 ng/mL) had a worse overall survival rate compared to the patients having CRC with low TEM1 concentration (<1.055 ng/mL). In conclusion, TEM1 can act as a potential diagnostic, progression, and prognostic serum biomarker for patients with CRC; TEM1 might be a good supplement for commonly used markers CEA and Ca 19-9.

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 poor prognosis. Detection of circulating microRNAs (miRNAs) is one of the liquid biopsy approaches. Numerous researches have suggested that some differentially expressed miRNAs may be promising diagnostic markers for PC, but the results varied among studies. The present study aimed 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 circulating miRNAs in differentiating PC 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. Circulating miRNAs also yielded an acceptable diagnostic accuracy for early-stage PC with SEN of 0.79 (0.76-0.82), SPE of 0.74 (0.68-0.79) and AUC of 0.81 (0.77-0.84). Conclusions: Circulating miRNAs exhibited a satisfactory diagnostic performance for PC, 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 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.

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