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 The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer

2021 ◽  
Vol 14 (3) ◽  
pp. 209
Author(s):  
Zachary Heinzman ◽  
Connor Schmidt ◽  
Marek K. Sliwinski ◽  
Nalin C. W. Goonesekere
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Early Stage ◽  
Dependent Manner ◽  
Strong Inhibitor ◽  
Tissue Samples ◽  
Reverse Transcription Pcr ◽  
Tumor Stages ◽  
Early Tumor

The high mortality rate for pancreatic cancer (PC) is due to the lack of specific symptoms at early tumor stages and a high biological aggressiveness. Reliable biomarkers and new therapeutic targets would help to improve outlook in PC. In this study, we analyzed the expression of GNMT in a panel of pancreatic cancer cell lines and in early-stage paired patient tissue samples (normal and diseased) by quantitative reverse transcription-PCR (qRT-PCR). We also investigated the effect of 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (PGG) as a therapeutic agent for PC. We find that GNMT is markedly downregulated (p < 0.05), in a majority of PC cell lines. Similar results are observed in early-stage patient tissue samples, where GNMT expression can be reduced by a 100-fold or more. We also show that PGG is a strong inhibitor of PC cell proliferation, with an IC50 value of 12 ng/mL, and PGG upregulates GNMT expression in a dose-dependent manner. In conclusion, our data show that GNMT has promise as a biomarker and as a therapeutic target for PC.

scholarly journals Separation and Identification of HSP-Associated Protein Complexes from Pancreatic Cancer Cell Lines Using 2D CN/SDS-PAGE Coupled with Mass Spectrometry

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Zhiyun Zhao ◽  
Hui Liu ◽  
Xinli Wang ◽  
Xiaodong Wang ◽  
Zhili Li
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Protein Function ◽  
Pancreatic Cancer Cell ◽  
Protein Complexes ◽  
Early Stage ◽  
Cancer Cell Lines ◽  
Building Models ◽  
Sds Page

Protein complexes are a cornerstone of many biological processes and together they form various types of molecular machinery. A broad understanding of these protein complexes is crucial for revealing and building models of protein function and regulation. Pancreatic cancer is a highly lethal disease which is difficult to diagnose at early stage and even more difficult to cure. In this study, we applied a gradient clear native gel system combined with subsequent second-dimensional SDS-PAGE to separate protein complexes from cell lysates of SW1990 and PANC-1 pancreatic cancer cell lines with different degrees of differentiation. Ten heat-shock-protein- (HSP-) associated protein complexes were separated and identified, and the differentially expressed proteins related to cancers were also found, such as HSP60, protein disulfide-isomerase A4 (ERp72), and transitional endoplasmic reticulum ATPase (TER ATPase).

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 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 Elevated Interleukin-6 Levels in the Circulation and Peritoneal Fluid of Patients with Ovarian Cancer as a Potential Diagnostic Biomarker: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 (12) ◽  
pp. 1335
Author(s):  
Hina Amer ◽  
Apriliana E. R. Kartikasari ◽  
Magdalena Plebanski
Keyword(s):  
Ovarian Cancer ◽  
Late Stage ◽  
Diagnostic Performance ◽  
Diagnostic Marker ◽  
Early Stage ◽  
Meta Analysis ◽  
Healthy Controls ◽  
Diagnostic Biomarker ◽  
The Mean ◽  
Higher Sensitivity

Ovarian cancer (OC) is one of the most lethal cancers, largely due to a late diagnosis. This study aimed to provide a comprehensive meta-analysis on the diagnostic performance of IL6 in the blood and ascites separately for advanced and early-stage OC. We included 37 studies with 6948 participants detecting serum or plasma IL6. The plasma/serum IL6 mean level in the late-stage OC was 23.88 pg/mL (95% CI: 13.84–41.23), and the early-stage OC was 16.67 pg/mL (95% CI: 510.06–27.61), significantly higher than the healthy controls at 3.96 pg/mL (95% CI: 2.02–7.73), but not significantly higher than those found in the controls with benign growths in the ovary, which was 9.63 pg/mL (95% CI: 4.16–22.26). To evaluate IL6 in ascites as a diagnostic marker, we included 26 studies with 1590 participants. The mean level of ascitic IL6 in the late-stage OC was 3676.93 pg/mL (95% CI: 1891.7–7146.7), and the early-stage OC was 1519.21 pg/mL (95% CI: 604.6–3817.7), significantly higher than the benign controls at 247.33 pg/mL (95% CI: 96.2–636.0). There was no significant correlation between the levels of circulating and ascitic IL6. When pooling all OC stages for analysis, we found that serum/plasma IL6 provided 76.7% sensitivity (95% CI: 0.71–0.92) and 72% specificity (95% CI: 0.64–0.79). Ascitic IL6 provided higher sensitivity at 84% (95% CI: 0.710–0.919) and specificity at 74% (95% CI: 0.646–0.826). This study highlights the utility of ascitic IL6 for early detection of OC.

scholarly journals LncRNA GAS8-AS1 is a Novel Prognostic and Diagnostic Biomarker for Pancreatic Cancer

2021 ◽  
Author(s):  
Ling Zhang ◽  
Miao Li ◽  
Lihong Deng ◽  
Dujiang Yang ◽  
Chao Yue ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Plasma Levels ◽  
Early Stage ◽  
Migration And Invasion ◽  
Cell Transfection ◽  
Healthy Controls ◽  
Overall Survival Rate ◽  
Diagnostic Biomarker ◽  
Real Time Quantitative Pcr

Abstract Background: LncRNA GAS8-AS1 inhibits thyroid carcinoma, but its function in other malignancies is unknown. The present study aimed to investigate the involvement of GAS8-AS1 in pancreatic cancer (PC). Methods: The present study included 68 PC patients (38 males and 30 females, 42- 66 years, 52.1±4.5) and 62 healthy volunteers (28 males and 24 females, 43- 67 years, 52.3 ±4.9). Real-time quantitative PCR, transient cell transfection and in vitro cell migration and invasion assay were applied for the research. In the present study we found that plasma GAS8-AS1 was lower in PC patients than in healthy controls. Downregulation of plasma GAS8-AS1 distinguished early stage PC patients from healthy controls. Results: Patients with low plasma levels of GAS8-AS1 showed significantly lower 5-year overall survival rate. Plasma levels of miR-1179 were also significantly lower in PC patients than in healthy controls, and were positively correlated with plasma levels of GAS8-AS1 only in PC patients. GAS8-AS1 overexpression resulted in the upregulation of miR-1179. MiR-1179 overexpression also led to the overexpression of GAS8-AS1. Overexpression of both GAS8-AS1 and miR-1179 led to inhibited migration and invasion of PC cells. Conclusions: Therefore, GAS8-AS1 may promote PC by positively interacting with miR-1179.

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 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer

2020 ◽  
Vol 4 (s1) ◽  
pp. 7-7
Author(s):  
Charles P Hinzman ◽  
Shivani Bansal ◽  
Yaoxiang Li ◽  
Partha Banerjee ◽  
Amrita Cheema
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Late Stage ◽  
Normal Cell ◽  
Normal Pancreas ◽  
Pancreas Cell ◽  
Potential Biomarkers

OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths by 2030. Though many other cancers have seen improvements in patient survival rates, patients diagnosed with PDAC have a 5-year survival rate of only ~9%. A major contributor to decreased survival is late-stage diagnosis of the disease. New methods of early detection are urgently needed. Extracellular vesicles (EVs) are secreted from cells of all tissue types into the circulation. EVs play important roles in a variety of diseases. They have shown to promote cancer progression and they are being studied as potential biomarkers for disease diagnosis. The purpose of this study was to perform qualitative and quantitative characterization of small-molecule profiles of EVs derived from various pancreatic cancer (PC) and normal pancreas cell lines, to provide proof-of-concept for evaluating the efficacy of leveraging EVs as potential biomarkers of PDAC. METHODS/STUDY POPULATION: EVs were isolated from the conditioned media of six PC and two normal pancreas cell lines using differential ultracentrifugation with filtration. EV enrichment was validated using quantitative ELISA, immunoblot and transmission electron microscopy. Targeted liquid chromatography coupled to mass spectrometry (LC-MS/MS) and untargeted (UPLC-QTOF-MS) metabolomics were used to analyze the biochemical composition of EVs. RESULTS/ANTICIPATED RESULTS: The biochemical profile of PC EVs was found to be significantly different from the profiles of normal cell EVs. Interestingly, amino acids were downregulated in PC EVs as compared to normal cell EVs. However, PC EVs were enriched in lactate and malate. PC EVs also had significant upregulation in other small molecules such as xanthosine, guanosine diphosphate and nicotinamide. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that the biochemical characterization of EVs using metabolomics has the potential to yield biomarkers which can delineate cancer cell-derived EVs from normal cell-derived EVs. Further work will test the clinical significance of these findings by similar analyses of plasma of PDAC patients. Furthermore, these profiles may be detectable before progression of the disease to late-stage PDAC, leading to the development of assays for earlier diagnosis in patients.

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

2019 ◽  
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 SEN, 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, 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 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 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 Abstract B20: Development and validation of diagnostic biomarker model for detection of early stage pancreatic cancer

2015 ◽  
Author(s):  
Ayumu Taguchi ◽  
Michela Capello ◽  
Yang Zhao ◽  
Ingrid Babel ◽  
Gary Goodman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Diagnostic Biomarker ◽  
Development And Validation
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