scholarly journals Molecular Approaches Using Body Fluid for the Early Detection of Pancreatic Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 375
Author(s):  
Kennichi Satoh
Keyword(s):  
Early Detection ◽  
Invasive Carcinoma ◽  
Early Stage ◽  
Genetic Alterations ◽  
Disease Stage ◽  
Ductal Adenocarcinoma ◽  
Genetic Changes ◽  
Non Invasive ◽  
Molecular Approaches ◽  
Cause Of Deaths

Pancreatic ductal adenocarcinoma (PDAC) is the most malignant form of gastrointestinal tumor and is the fourth leading cause of deaths due to cancer in Japan. This cancer shows a poor outcome due to the difficulty of its early diagnosis and its rapid growth. Once this disease becomes clinically evident, it is frequently accompanied by distant metastasis at the time of diagnosis. A recent multicenter study in Japan revealed that patients with the early stage of this disease (stage 0 and I) showed favorable prognosis after surgical resection, indicating the importance of early detection for improvement of PDAC prognosis. PDAC develops through a stepwise progression from the precursor lesion, and over the last few decades molecular analyses have shown the detailed genetic alterations that occur in this process. Since advances in molecular technologies have enabled the detection of genetic changes from a very small quantity of samples, a large number of non-invasive molecular approaches have been utilized in an attempt to find precursor or non-invasive carcinoma lesions. In this review, the current efforts in terms of the molecular approaches applied for the early detection of PDAC—especially using body fluids such as pancreatic juice, blood, and saliva—are summarized.

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 Multianalyte Tests for the Early Detection of Cancer: Speedbumps and Barriers

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Michael A. Tainsky ◽  
Madhumita Chatterjee ◽  
Nancy K. Levin ◽  
Sorin Draghici ◽  
Judith Abrams
Keyword(s):  
Early Detection ◽  
Tumor Antigens ◽  
Early Stage ◽  
False Negative ◽  
Clinical Intervention ◽  
Screening Tests ◽  
Molecular Event ◽  
Non Invasive ◽  
In Vitro Diagnostic

It has become very clear that a single molecular event is inadequate to accurately predict the biology (or pathophysiology) of cancer. Furthermore, using any single molecular event as a biomarker for the early detection of malignancy may not comprehensively identify the majority of individuals with that disease. Therefore, the fact that technologies have arisen that can simultaneously detect several, possibly hundreds, of biomarkers has propelled the field towards the development of multianalyte-based in vitro diagnostic early detection tests for cancer using body fluids such as serum, plasma, sputum, saliva, or urine. These multianalyte tests may be based on the detection of serum autoantibodies to tumor antigens, the presence of cancer-related proteins in serum, or the presence of tumor-specific genomic changes that appear in plasma as free DNA. The implementation of non-invasive diagnostic approaches to detect early stage cancer may provide the physician with evidence of cancer, but the question arises as to how the information will affect the pathway of clinical intervention. The confirmation of a positive result from an in vitro diagnostic cancer test may involve relatively invasive procedures to establish a true cancer diagnosis. If in vitro diagnostic tests are proven to be both specific, i.e. rarely produce false positive results due to unrelated conditions, and sufficiently sensitive, i.e. rarely produce false negative results, then such screening tests offer the potential for early detection and personalized therapeutics using multiple disease-related targets with convenient and non-invasive means. Here we discuss the technical and regulatory barriers inherent in development of clinical multianalyte biomarker assays.

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 MicroRNA-21 Is Induced Early in Pancreatic Ductal Adenocarcinoma Precursor Lesions

2010 ◽  
Vol 56 (4) ◽  
pp. 603-612 ◽  
Author(s):  
Maël Chalret du Rieu ◽  
Jérôme Torrisani ◽  
Janick Selves ◽  
Talal Al Saati ◽  
Anny Souque ◽  
...  
Keyword(s):  
Early Detection ◽  
Mouse Model ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Survival Rates ◽  
Ductal Adenocarcinoma ◽  
Early Event ◽  
Precursor Lesions ◽  
Tissue Samples ◽  
Ductal Cells

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) has the poorest overall prognosis among gastrointestinal cancers; however, curative resection in early-stage PDAC greatly improves survival rates, indicating the importance of early detection. Because abnormal microRNA production is commonly detected in cancer, we investigated noninvasive precursor pancreatic intraepithelial neoplasia (PanIN) lesions for microRNA production as a potential early biomarker of PDAC. Methods: Pathologists identified and classified ductal lesions. We extracted total RNA from laser-capture microdissected PanIN tissue samples from a conditional KRAS(G12D) mouse model (n = 29) or of human origin (n = 38) (KRAS is v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). MicroRNA production was quantified by quantitative real-time PCR. Internal controls included 5S and U6 RNAs. Results: Production of microRNAs miR-21, miR-205, and miR-200 paralleled PanIN progression in the KRAS(G12D) mouse model, compared with microRNA production in samples of nonpathologic ducts. miR-21 demonstrated the highest relative concentrations in the precursor lesions. Interestingly, miR-205 and miR-21 up-regulation preceded phenotypic changes in the ducts. The production of microRNAs miR-21, miR-221, miR-222, and let-7a increased with human PanIN grade, with peak production occurring in hyperplastic PanIN-2/3 lesions. In situ hybridization analysis indicated miR-21 production to be concentrated in pathologic ductal cells. miR-21 production was regulated by KRAS(G12D) and epidermal growth factor receptor in PDAC-derived cell lines. Conclusions: Aberrant microRNA production is an early event in the development of PanIN. Our findings indicate that miR-21 warrants further investigation as a marker for early detection of PDAC.

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.

Non-invasive diagnosis and tracking of tumor evolution by targeted sequencing of circulating tumor DNA in metastatic pancreatic cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15769-e15769
Author(s):  
Thomas Seufferlein ◽  
Andreas W. Berger ◽  
Daniel Schwerdel ◽  
Thomas Jens Ettrich ◽  
Stefan A. Schmidt ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Early Stage ◽  
Therapy Monitoring ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Tumor Evolution ◽  
Imaging Data ◽  
Non Invasive ◽  
Outcome Monitoring ◽  
Tumor Dna

e15769 Background: Treatment of stage IV pancreatic ductal adenocarcinoma (PDAC) has made substantial progress over the last years, therapy monitoring still is at an early stage. This could be substantially supported by tools that allow to establish and monitor the molecular setup of the tumor even during treatment. In particular, non-invasive approaches are desirable. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal. Methods: We analyzed a cohort of 20 patients with histologically confirmed metastatic PDAC (mPDAC) prior to and during palliative treatment including disease progression. ctDNA and corresponding tumor tissue were analyzed by targeted NGS and droplet digital PCR for the 7 most frequently mutated genes in PDAC ( TP53, SMAD4, CDKN2A, KRAS, APC, ATM, FBXW7). Findings were correlated with clinical and imaging data to establish its prognostic and predictive value. Results: ctDNA was analyzed at baseline prior to initiation of the respective line of treatment. Mutations in either of the genes examined were detectable in 15/20 patients (75%). Tissue-blood concordance was 80% in therapy naïve patients. 96% of mutations in ctDNA of therapy naïve patients were in KRAS and/or TP53. The combined mutated allele frequencies (CMAF) of theese 2 genes significantly decreased (p = 0.0173) during therapy and increased at progression (p = 0.0145) across all treatment lines. By sequential ctDNA analyses we detected a change in the mutational landscape compared to the respective baseline ctDNA status in 7/11 patients during 1st line, in 3/7 patients during 2nd line and 2/2 patients during 3rdline treatment. In therapy naïve patients, the decline of the CMAF during therapy significantly correlated with progression-free survival (p = 0.0013). Conclusions: Molecular genotyping of ctDNA in mPDAC patients proved to be feasible and there was a high concordance between tumor tissue and ctDNA. The molecular genotype changed significantly during treatment and changes correlated with outcome. Monitoring of ctDNA may enable to adapt therapeutic strategies to the specific molecular changes present at a certain time during treatment of mPDAC.

scholarly journals The detection of oral pre- malignant lesions with an autofluorescence based imaging system (VELscopeTM) – a single blinded clinical evaluation

2013 ◽  
Vol 9 (1) ◽  
Author(s):  
Henning Hanken ◽  
Juliane Kraatz ◽  
Ralf Smeets ◽  
Max Heiland ◽  
Marco Blessmann ◽  
...  
Keyword(s):  
Early Detection ◽  
White Light ◽  
Imaging System ◽  
Early Stage ◽  
Premalignant Lesions ◽  
Diagnostic Strategies ◽  
Non Invasive ◽  
Invasive Test ◽  
Malignant Lesions ◽  
Group 2

Abstract Objective The disease specific five-year survival rate especially for patients with advanced oral cancer has not improved significantly over the period of time. The most effective way of combating this dilemma is an early detection, diagnosis and eradication of early-stage lesions and their precursors. The use of VELscope® using an autofluorescence as a diagnostic tool might be useful in early detection of oral malignant lesions. Materials and methods 120 patients with suspicious oral premalignant lesions were examined with two examination methods. They were randomly divided into two groups. Group 1 was examined conventional with white-light and group 2 was examined additionally to the white-light-examination with an autofluorescence visualization device, VELscope®. Biopsies were obtained from all suspicious areas identified in both examination groups (n = 52). The diagnostic strategies were compared regarding sensitivity and specificity. Results Based upon the result, use of the VELscope® leads to a higher sensitivity (22.0%), but regarding specificity the additional use of the VELscope® is inferior (8.4%). Conclusion The VELscope device is a simple, non-invasive test of the oral mucosa, which can help the experienced clinician to find oral precursor malignant lesions.

scholarly journals ctDNA in Breast Milk for Early Detection of Pregnancy Associated Breast Cancer

2021 ◽  
Author(s):  
Miriam Sanso ◽  
Cristina Saura ◽  
Carolina Ortiz ◽  
Enrique Arenas Lahuerta ◽  
Judit Matito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Milk ◽  
Early Detection ◽  
Early Stage ◽  
Early Stage Disease ◽  
Genetic Profiling ◽  
Non Invasive ◽  
Milk Serum ◽  
Stage Disease ◽  
Localized Disease

Abstract Pregnancy associated breast cancer (PABC) is an overall poor prognosis group compared to non-PABC breast cancer (BC), mainly due to late diagnosis. Effective screening approaches for early detection may improve its outcome. For the first time, we demonstrate the presence of cell-free tumor DNA (ctDNA) in the breast milk serum (sBM) of PABC in patients with early-stage disease and its ability to recapitulate somatic mutations present in the primary tumor. Moreover, our results demonstrate that sBM robustly surpasses plasma for tumor genetic profiling due to a prevalent shedding of ctDNA into the sBM in localized disease, as well as increased total cell-free DNA (cfDNA) abundance and integrity. Thus, we propose sBM as a potential new non-invasive liquid biopsy for a prompt detection of PABC.

scholarly journals Circulating Exosomal miRNAs as Biomarkers in Epithelial Ovarian Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1433
Author(s):  
Meng-Shin Shiao ◽  
Jia-Ming Chang ◽  
Arb-Aroon Lertkhachonsuk ◽  
Naparat Rermluk ◽  
Natini Jinawath
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Epithelial Ovarian Cancer ◽  
Early Stage ◽  
Cell Communication ◽  
Biological Molecules ◽  
Non Invasive ◽  
Exosomal Mirnas ◽  
Endogenous Reference ◽  
Treatment Responses

Failure to detect early-stage epithelial ovarian cancer (EOC) is a major contributing factor to its low survival rate. Increasing evidence suggests that different subtypes of EOC may behave as distinct diseases due to their different cells of origins, histology and treatment responses. Therefore, the identification of EOC subtype-specific biomarkers that can early detect the disease should be clinically beneficial. Exosomes are extracellular vesicles secreted by different types of cells and carry biological molecules, which play important roles in cell-cell communication and regulation of various biological processes. Multiple studies have proposed that exosomal miRNAs present in the circulation are good biomarkers for non-invasive early detection of cancer. In this review, the potential use of exosomal miRNAs as early detection biomarkers for EOCs and their accuracy are discussed. We also review the differential expression of circulating exosomal miRNAs and cell-free miRNAs between different biofluid sources, i.e., plasma and serum, and touch on the issue of endogenous reference miRNA selection. Additionally, the current clinical trials using miRNAs for detecting EOCs are summarized. In conclusion, circulating exosomal miRNAs as the non-invasive biomarkers have a high potential for early detection of EOC and its subtypes, and are likely to be clinically important in the future.

scholarly journals Usefulness of Monitoring Circulating Tumor Cells as a Therapeutic Biomarker in Melanoma with BRAF Mutation

2020 ◽  
Author(s):  
Ryuhei Okuyama ◽  
Yukiko Kiniwa ◽  
Kenta Nakamura ◽  
Asuka Mikoshiba ◽  
Atsuko Ashida ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Drug Response ◽  
Early Stage ◽  
Stage Iv ◽  
Mek Inhibitor ◽  
Disease Stage ◽  
Mek Inhibitors ◽  
Non Invasive

Abstract Background: Circulating tumor cells (CTCs) are non-invasive biomarkers that could be used to characterize changes in tumors. In this study, we monitored the number of CTCs, as well as the BRAF genotype of individual CTCs. Methods: CTCs were isolated from peripheral blood using a high-density dielectrophoretic microwell array, followed by labeling with melanoma-specific markers (MART-1 and/or gp100) and a leukocyte marker (CD45). Results: Examination of patients with stage 0–III melanoma detected CTCs even in patients with early disease (stage 0 or I). Next, we analyzed CTCs in five patients with stage IV melanoma during treatment with BRAF/MEK inhibitors. The number of CTCs fluctuated in association with the drug response in four of the five patients, suggesting that the total number of CTCs usually reflected the drug response. Interestingly, one of those patients had CTCs with seven different BRAF genotypes, and the mutated CTCs disappeared upon treatment with BRAF/MEK inhibitors, except for those harboring BRAFA598V.Conclusions: CTCs are present even in the early stage of melanoma, and the number of CTCs seems to reflect drug response during treatment with BRAF/MEK inhibitors. Furthermore, genetic heterogeneity of BRAF may contribute to drug resistance of BRAF/MEK inhibitor. Our findings demonstrate the usefulness of CTC analysis in melanoma for monitoring targeted therapies and understanding mechanism of drug resistance.

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