Current status of molecular diagnostic approaches using liquid biopsy

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, and developing an efficient and reliable approach for its early-stage diagnosis is urgently needed. Precancerous lesions of PDAC, such as pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN), arise through multiple steps of driver gene alterations in KRAS, TP53, CDKN2A, SMAD4, or GNAS. Hallmark mutations play a role in tumor initiation and progression, and their detection in bodily fluids is crucial for diagnosis. Recently, liquid biopsy has gained attention as an approach to complement pathological diagnosis, and in addition to mutation signatures in cell-free DNA, cell-free RNA, and extracellular vesicles have been investigated as potential diagnostic and prognostic markers. Integrating such molecular information to revise the diagnostic criteria for pancreatic cancer can enable a better understanding of the pathogenesis underlying inter-patient heterogeneity, such as sensitivity to chemotherapy and disease outcomes. This review discusses the current diagnostic approaches and clinical applications of genetic analysis in pancreatic cancer and diagnostic attempts by liquid biopsy and molecular analyses using pancreatic juice, duodenal fluid, and blood samples. Emerging knowledge in the rapidly advancing liquid biopsy field is promising for molecular profiling and diagnosing pancreatic diseases with significant diversity.

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

“…A large meta-analysis that included 57 studies representing 3285 patients with pancreatic cancer and 37 studies representing 1882 cases with benign pancreatic disease confirmed an 80% sensitivity and specificity for CA 19-9 (with a 37 U/mL cutoff) and a sensitivity of 45% and specificity of 85% for CEA (5 ng/mL cutoff) [ 30 ]. CA 19-9 can be elevated in other malignancies and benign hepato-pancreaticobiliary conditions, contributing to lower diagnostic accuracy for PDAC [ 31 ]. Neither of these markers has the necessary accuracy to screen asymptomatic populations, and they are currently used in clinical context in combination with imaging modalities to guide diagnostic and treatment decisions.…”

Correlation between main pancreatic duct diameter measurements: Special pancreatic ultrasonography versus magnetic resonance cholangiopancreatography

“…[5,6] The prognosis of PC remains dismal; therefore, early detection is important. [7][8][9][10] Recently, monitoring individuals at high risk for PC has been of high importance. [11][12][13][14] Magnetic resonance cholangiopancreatography (MRCP) is a valuable imaging modality that offers clear visualization without using harmful ionizing radiation, thus enhancing patient safety.…”

Oil blotting paper for formalin fixation increases endoscopic ultrasound‐guided tissue acquisition‐collected sample volumes on glass slides

“… 16 , 17 , 18 , 19 In clinical practice, (CGP) tests have been reported to be beneficial for patients with pancreatic cancer. 20 , 21 , 22 , 23 , 24 Notably, in Japan, CGP tests have been covered by Japanese health insurance since June 2019, highlighting the need for obtaining sufficient samples via EUS‐TA.…”

“…Moreover, pembrolizumab has been recently recommended for tumors exhibiting high microsatellite instability or a high tumor mutation burden; however, its efficacy is limited to a small number of cases 16–19 . In clinical practice, (CGP) tests have been reported to be beneficial for patients with pancreatic cancer 20–24 . Notably, in Japan, CGP tests have been covered by Japanese health insurance since June 2019, highlighting the need for obtaining sufficient samples via EUS‐TA.…”