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.

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 Outcomes of Patients with Initially Locally Advanced Pancreatic Adenocarcinoma who did not Benefit from Resection: A Prospective Cohort Study

2020 ◽  
Author(s):  
Jonathan Garnier ◽  
Jacques Ewald ◽  
Ugo Marchese ◽  
Marine Gilabert ◽  
Simon Launay ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Pancreatic Adenocarcinoma ◽  
Metastatic Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Wilcoxon Test ◽  
Stepwise Logistic Regression ◽  
Short Term Treatment ◽  
Locally Advanced Pancreatic Adenocarcinoma ◽  
Advanced Pancreatic Adenocarcinoma

Abstract Background: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. Methods: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. Results: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR)=1.2, 95% confidence interval: 0.86–1.6, P =.03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0–1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR=1.38, 95% confidence interval: 1–1.9, P <.01) and limited short-term treatment-related toxicity. Conclusions: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

scholarly journals Outcomes of Patients with Initially Locally Advanced Pancreatic Adenocarcinoma who did not Benefit from Resection: A Prospective Cohort Study

2020 ◽  
Author(s):  
Jonathan Garnier ◽  
Jacques Ewald ◽  
Ugo Marchese ◽  
Marine Gilabert ◽  
Simon Launay ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Pancreatic Adenocarcinoma ◽  
Metastatic Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Wilcoxon Test ◽  
Stepwise Logistic Regression ◽  
Short Term Treatment ◽  
Locally Advanced Pancreatic Adenocarcinoma ◽  
Advanced Pancreatic Adenocarcinoma

Abstract Background: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. Methods: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. Results: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR)=1.2, 95% confidence interval: 0.86–1.6, P =.03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0–1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR=1.38, 95% confidence interval: 1–1.9, P <.01) and limited short-term treatment-related toxicity. Conclusions: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

Differential Expression of Metastasis-Associated Genes in Papilla of Vater and Pancreatic Cancer Correlates With Disease Stage

2001 ◽  
Vol 19 (9) ◽  
pp. 2422-2432 ◽  
Author(s):  
Helmut Friess ◽  
Xiao-Zhong Guo ◽  
Adrien A. Tempia-Caliera ◽  
Akira Fukuda ◽  
Marcus E. Martignoni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
In Situ Hybridization ◽  
Early Stage ◽  
Expression Patterns ◽  
Tumor Biology ◽  
Disease Stage ◽  
Papilla Of Vater ◽  
Advanced Tumor ◽  
Tumor Stages

PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer. PATIENTS AND METHODS: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins. RESULTS: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages. CONCLUSION: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities.

scholarly journals Coupled liquid biopsy and bioinformatics for pancreatic cancer early detection and precision prognostication

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jun Hou ◽  
XueTao Li ◽  
Ke-Ping Xie
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Residual Disease ◽  
Liquid Biopsies ◽  
Tissue Samples ◽  
Complete Representation ◽  
Minimal Invasiveness ◽  
Cancer Early Detection ◽  
Pancreatic Cancer Cells ◽  
Repeated Sampling

AbstractEarly detection and diagnosis are the key to successful clinical management of pancreatic cancer and improve the patient outcome. However, due to the absence of early symptoms and the aggressiveness of pancreatic cancer, its 5-year survival rate remains below 5 %. Compared to tissue samples, liquid biopsies are of particular interest in clinical settings with respect to minimal invasiveness, repeated sampling, complete representation of the entire or multi-site tumor bulks. The potential of liquid biopsies in pancreatic cancer has been demonstrated by many studies which prove that liquid biopsies are able to detect early emergency of pancreatic cancer cells, residual disease, and recurrence. More interestingly, they show potential to delineate the heterogeneity, spatial and temporal, of pancreatic cancer. However, the performance of liquid biopsies for the diagnosis varies largely across different studies depending of the technique employed and also the type and stage of the tumor. One approach to improve the detect performance of liquid biopsies is to intensively inspect circulome and to define integrated biomarkers which simultaneously profile circulating tumor cells and DNA, extracellular vesicles, and circulating DNA, or cell free DNA and proteins. Moreover, the diagnostic validity and accuracy of liquid biopsies still need to be comprehensively demonstrated and validated.

scholarly journals Computational Analysis of Specific MicroRNA Biomarkers for Noninvasive Early Cancer Detection

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Tianci Song ◽  
Yanchun Liang ◽  
Zhongbo Cao ◽  
Wei Du ◽  
Ying Li
Keyword(s):  
Early Detection ◽  
Cancer Detection ◽  
Target Gene ◽  
Complex Disease ◽  
Early Stage ◽  
Function Analysis ◽  
Expression Patterns ◽  
Potential Candidate ◽  
Cancer Types ◽  
And Function

Cancer is a complex disease residing in various tissues of human body, accompanied with many abnormalities and mutations in genomes, transcriptome, and epigenome. Early detection plays a crucial role in extending survival time of all major cancer types. Recent advances in microarray and sequencing techniques have given more support to identifying effective biomarkers for early detection of cancer. MicroRNAs (miRNAs) are more and more frequently used as candidates for biomarkers in cancer related studies due to their regulation of target gene expression. In this paper, the comparative analysis is used to discover miRNA expression patterns in cancer versus normal samples on early stage of eight prevalent cancer types. Our work focuses on the specific miRNAs biomarkers identification and function analysis. Several identified miRNA biomarkers in this paper are matched well with those reported in existing researches, and most of them could serve as potential candidate indicators for clinical early diagnosis applications.

scholarly journals Comparison of the Diagnostic Efficiency of Radial- and Convex-Arrayed Echoendoscopes for Indirect Findings of Pancreatic Cancer: A Retrospective Comparative Study Using Propensity Score Method

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1217
Author(s):  
Yuki Ishikawa-Kakiya ◽  
Hirotsugu Maruyama ◽  
Kei Yamamoto ◽  
Masafumi Yamamura ◽  
Kojiro Tanoue ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Confidence Interval ◽  
Comparative Study ◽  
Odds Ratio ◽  
Detection Rate ◽  
Early Stage ◽  
Univariate Analysis ◽  
Diagnostic Efficiency ◽  
Propensity Score Method ◽  
Branch Duct

Endoscopic ultrasonography (EUS) is useful for detecting early-stage pancreatic cancer. Because the detection of small lesions is difficult, it is important to detect indirect findings, namely caliber change, retention cysts, and dilatation of the branch duct, during the procedure. Although two types of EUS endoscopes are frequently used, there is no comparative study on their efficacy for detecting indirect findings. Therefore, we aimed to compare the diagnostic efficacy of these two types for indirect findings. We retrospectively analyzed 316 consecutive patients who had undergone EUS for pancreaticobiliary disease at a single center between January 2017 and December 2018. The main outcome was the detection rate of indirect findings and its comparison between the two echoendoscope types. This outcome was achieved using the inverse probability of treatment weighting (IPTW) analysis. The detection rate of indirect findings was higher for the radial-arrayed endoscope than for the convex-arrayed echoendoscope (9.2% vs. 2.3% (p = 0.02)). The univariate analysis also revealed that the radial-arrayed echoendoscope was significantly superior to the convex-arrayed echoendoscope in terms of the detection of indirect findings (odds ratio, 5.94; 95% confidence interval, 1.68–21.10; p = 0.01) after IPTW. After adjustment for magnetic resonance imaging (MRI) and computed tomography (CT), radial-arrayed echoendoscope remained an independent factor for indirect finding detection (odds ratio, 6.04; 95% confidence interval, 1.74–21.00; p = 0.01). Finally, five patients who had indirect EUS findings were diagnosed with pancreatic cancer. Our results indicate that the radial-arrayed echoendoscope is useful for the detection of indirect findings.

Green synthesis of nanomaterials for early lung cancer detection

2018 ◽  
pp. 1-1
Keyword(s):  
Lung Cancer ◽  
Green Synthesis ◽  
Cancer Detection ◽  
World Wide ◽  
Early Stage ◽  
Age Groups ◽  
Early Lung Cancer ◽  
Lung Cancer Detection ◽  
Synthesis Of Nanomaterials

Lung cancer is the foremost cause of cancer-related deaths world-wide [1]. It affects 100,000 Americans of the smoking population every year of all age groups, particularly those above 50 years of the smoking population [2]. In India, 51,000 lung cancer deaths were reported in 2012, which include 41,000 men and 10,000 women [3]. It is the leading cause of cancer deaths in men; however, in women, it ranked ninth among all cancerous deaths [4]. It is possible to detect the lung cancer at a very early stage, providing a much higher chance of survival for the patients.

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