Protein biomarkers point to early stage pancreatic cancer

2008 ◽  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Protein Biomarkers

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

The Increasing Proportion of Early-Stage Pancreatic Cancer between 2004–2013: A SEER Analysis

2021 ◽  
Vol 39 (3) ◽  
pp. 229-234
Author(s):  
Sven P Oman ◽  
Juan E Corral ◽  
John Stauffer ◽  
Massimo Raimondo ◽  
Kabir Mody ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage

scholarly journals Detection of KRAS Mutations in Circulating Tumor DNA by Digital PCR in Early Stages of Pancreatic Cancer

2016 ◽  
Vol 62 (11) ◽  
pp. 1482-1491 ◽  
Author(s):  
Nora Brychta ◽  
Thomas Krahn ◽  
Oliver von Ahsen
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Surgical Removal ◽  
Plasma Samples ◽  
Kras Mutations ◽  
Detection Rates ◽  
Early Stages ◽  
Tumor Dna

Abstract BACKGROUND Since surgical removal remains the only cure for pancreatic cancer, early detection is of utmost importance. Circulating biomarkers have potential as diagnostic tool for pancreatic cancer, which typically causes clinical symptoms only in advanced stage. Because of their high prevalence in pancreatic cancer, KRAS proto-oncogene, GTPase [KRAS (previous name: Kirsten rat sarcoma viral oncogene homolog)] mutations may be used to identify tumor-derived circulating plasma DNA. Here we tested the diagnostic sensitivity of chip based digital PCR for the detection of KRAS mutations in circulating tumor DNA (ctDNA) in early stage pancreatic cancer. METHODS We analyzed matched plasma (2 mL) and tumor samples from 50 patients with pancreatic cancer. Early stages (I and II) were predominant (41/50) in this cohort. DNA was extracted from tumor and plasma samples and tested for the common codon 12 mutations G12D, G12V, and G12C by chip-based digital PCR. RESULTS We identified KRAS mutations in 72% of the tumors. 44% of the tumors were positive for G12D, 20% for G12V, and 10% for G12C. One tumor was positive for G12D and G12V. Analysis of the mutations in matched plasma samples revealed detection rates of 36% for G12D, 50% for G12V, and 0% for G12C. The detection appeared to be correlated with total number of tumor cells in the primary tumor. No KRAS mutations were detected in 20 samples of healthy control plasma. CONCLUSIONS Our results support further evaluation of tumor specific mutations as early diagnostic biomarkers using plasma samples as liquid biopsy.

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 Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiang Chen ◽  
Hongyu Li ◽  
Wenda Xu ◽  
Xiaozhong Guo
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Potential Role ◽  
Early Stage ◽  
Serum Levels ◽  
Diagnostic Efficacy ◽  
Diagnostic Biomarkers ◽  
The Poor

Abstract Background Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9. Methods ATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94). Results Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012). Conclusion Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.

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.

Virus induced hepatocellular carcinoma (HCC) and protein biomarkers

2021 ◽  
Author(s):  
Hamza Abbas Jaffari ◽  
Sumaira Mazhar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Imaging Techniques ◽  
Disease Diagnosis ◽  
Protein Biomarkers ◽  
Early Disease ◽  
Detection Systems ◽  
Non Invasive ◽  
Viral Hepatitis B ◽  
Current Article

Hepatocellular carcinoma (HCC) is a standout amongst the most widely recognized cancers around the world, and just as the alcoholic liver disease it is also progressed by extreme viral hepatitis B or C. At the early stage of the disease, numerous patients are asymptomatic consequently late diagnosis of HCC occurs resulting in expensive surgical resection or transplantation. On the basis of the alpha fetoprotein (AFP) estimation, combined with the ultrasound and other sensitive imaging techniques used, the non-invasive detection systems are available. For early disease diagnosis and its use in the effective treatment of HCC patients, the identification of HCC biomarkers has provided a breakthrough utilizing the molecular genetics and proteomics. In the current article, most recent reports on the protein biomarkers of HBV or HCV-related HCC and their co-evolutionary association with liver cancer are reviewed.

Sign in / Sign up

Export Citation Format

Share Document