A Comprehensive Review of the Potential Role of Liquid Biopsy as a Diagnostic, Prognostic, and Predictive Biomarker in Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma is one of the most lethal malignant diseases, with a mortality rate being close to incidence. Due to its heterogeneity and plasticity, as well as the lack of distinct symptoms in the early phases, it is very often diagnosed at an advanced stage, resulting in poor prognosis. Traditional tissue biopsies remain the gold standard for making a diagnosis, but have an obvious disadvantage in their inapplicability for frequent sampling. Blood-based biopsies represent a non-invasive method which potentially offers easy and repeated sampling, leading to the early detection and real-time monitoring of the disease and hopefully an accurate prognosis. Given the urgent need for a reliable biomarker that can estimate a patient’s condition and response to an assigned treatment, blood-based biopsies are emerging as a potential new tool for improving patients’ survival and surveillance. In this article, we discuss the current advances and challenges in using liquid biopsies for pancreatic cancer, focusing on circulating tumour DNA (ctDNA), extracellular vesicles (EVs), and circulating tumour cells (CTCs), and compare the performance and reliability of different biomarkers and combinations of biomarkers.

Analytical platform to validate microRNA biomarkers for cancer or disease with practically 100% sensitivity and specificity

“…Most adults undergo an annual or biannual physical medical examination that does not include a multi-cancer test. Specialized tests are available for some prevalent cancer indications, but they are invasive, often painful, and can lead to unacceptable false-positive or false-negative results [4][5][6][7][8][9].…”

“…because of their low positive predictive value (PPV) [8,9]. A definitive diagnosis requires a series of imaging scans, blood tests, and biopsies, which are typically performed after the appearance of symptoms.…”

“…miR-21, miR-375 and miR-141 copies in cancers were 1.8-fold overexpressed, exhibited zero overlap with healthy samples and had a p value of 1.6x10 -22 , tentatively validating each miRNA as a cancer biomarker. miR-15b was confirmed to be cancer-independent, whereas let-7b appeared to be a cancer biomarker for prostate and breast cancer, but not for pancreatic cancer.because of their low positive predictive value (PPV) [8,9]. A definitive diagnosis requires a series of imaging scans, blood tests, and biopsies, which are typically performed after the appearance of symptoms.…”

High Sensitivity and Specificity Platform to Validate MicroRNA Biomarkers in Cancer and Human Diseases

“…Most adults undergo an annual or biannual physical medical examination that does not include a multi-cancer test. Specialized tests are available for some prevalent cancer indications, but they are invasive, often painful, and can lead to unacceptable false-positive or false-negative results [ 4 , 5 , 6 , 7 , 8 , 9 ]. Rigorous observational studies in Europe failed to determine the effects of mammography screening.…”

“…No single diagnostic test is available for pancreatic cancer. Serum levels of the antigen CA 19-9 higher than 37 U/mL are exploited for the diagnosis of pancreatic cancer in symptomatic patients, but they are not useful as screening markers in asymptomatic individuals because of their low positive predictive value (PPV) [ 8 , 9 ]. A definitive diagnosis requires a series of imaging scans, blood tests, and biopsies, which are typically performed after the appearance of symptoms.…”