Plasma extracellular vesicle long RNA profiling identifies a diagnostic signature for the detection of pancreatic ductal adenocarcinoma

Abstract

ObjectivePancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose at resectable stage. Recent studies have suggested that extracellular vesicles (EVs) contain long RNAs. The aim of this study was to develop a diagnostic (d-)signature for the detection of PDAC based on EV long RNA (exLR) profiling.DesignWe conducted a case-control study with 501 participants, including 284 patients with PDAC, 100 patients with chronic pancreatitis (CP) and 117 healthy subjects. The exLR profile of plasma samples was analysed by exLR sequencing. The d-signature was identified using a support vector machine algorithm and a training cohort (n=188) and was validated using an internal validation cohort (n=135) and an external validation cohort (n=178).ResultsWe developed a d-signature that comprised eight exLRs, including FGA, KRT19, HIST1H2BK, ITIH2, MARCH2, CLDN1, MAL2 and TIMP1, for PDAC detection. The d-signature showed high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.960, 0.950 and 0.936 in the training, internal validation and external validation cohort, respectively. The d-signature was able to identify resectable stage I/II cancer with an AUC of 0.949 in the combined three cohorts. In addition, the d-signature showed superior performance to carbohydrate antigen 19-9 in distinguishing PDAC from CP (AUC 0.931 vs 0.873, p=0.028).ConclusionThis study is the first to characterise the plasma exLR profile in PDAC and to report an exLR signature for the detection of pancreatic cancer. This signature may improve the prognosis of patients who would have otherwise missed the curative treatment window.

An Integrated Meta-Analysis of Secretome and Proteome Identify Potential Biomarkers of Pancreatic Ductal Adenocarcinoma

“…However, the combination of both LCN2 and TIMP1 with miR-196b was able to distinguish high-grade lesions and stage I from controls with absolute sensitivity and specificity [174]. Also, in accordance with our data, plasma extracellular vesicle long RNA profiling has identified a diagnostic signature, which includes the TIMP1 transcript, for the detection of pancreatic cancer [175]. This increased detection of TIMP1 transcript and protein might be partially explained by the effects of miRNAs such as miR-221/222 and miR-21.…”

Development of a Prognostic Five-Gene Signature with Radiotherapy Guidance Significance for Diffuse Lower-Grade Glioma Patients Based on Large-Scale Sequencing Data

“…H2B clustered histone 12(H2BC12 or HIST1H2BK) is a replication-dependent histone and belongs to the histone H2B family. The prognostic role of HIST1H2BK was identi ed in ovarian cancer [28], breast cancer [29] and pancreatic ductal adenocarcinoma [30].Although we had some ndings on the function of the ve prognostic genes by KEGG and GO analysis, further functional exploration of these genes is needed.…”

Dynamic plasma extracellular vesicle long RNA profiling changes during the peri-operative period

“…EVs contain a large number of valuable and functional exLRs [16,17]. In the current study, exLRs sequencing (exLR-seq) was performed on plasma samples collected from 3 CRC patients at 4 speci c time points (before surgery [T1], after extubation [T2], 1 day after surgery [T3], and 3 days after surgery [T4]) and produced a catalog of blood exLRs, which includes su cient species of mRNA and lncRNA to investigate the potential role for the progression of CRC to detect the effects of surgical stress on the exLR expression pro le.…”