PDAC - Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
pancreatic ductal adenocarcinoma, exosomal miRNA, early liver metastasis, liquid biopsy, exosome
Brief summary
Early liver metastasis (Early-LiM) is the most significant prognostic factor in pancreatic ductal adenocarcinoma (PDAC) and is thought to originate from occult micrometastases present at the time of surgery. Reliable preoperative detection of such lesions remains an unmet clinical need. The EXELiM study aims to develop and validate a circulating exosomal microRNA (exo-miRNA)-based liquid biopsy assay to accurately identify PDAC patients at high risk of occult liver metastasis before surgery. By integrating machine learning with multi-institutional plasma exosome profiling, this study seeks to enable biology-driven patient stratification and guide treatment sequencing toward precision oncology.
Detailed description
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human malignancies, with a 5-year overall survival rate below 10%. Even after curative-intent pancreatectomy, over 70% of patients experience disease recurrence, with early liver metastasis (within six months postoperatively) representing the most aggressive and fatal pattern. Emerging evidence indicates that pancreatic tumors release exosomes that modulate the liver microenvironment, establishing a premetastatic niche that facilitates early colonization. We hypothesize that circulating exosomal microRNAs reflect these biological processes and can serve as non-invasive biomarkers for detecting occult liver metastasis. In this multi-center observational study, preoperative plasma-derived exosomes from PDAC patients are analyzed using next-generation small RNA sequencing and validated by RT-qPCR. A machine learning model is employed to integrate exo-miRNA expression profiles and clinical variables, yielding a predictive score for early liver metastasis risk. The study evaluates the diagnostic accuracy, prognostic utility, and clinical benefit of the exo-miRNA panel compared to conventional biomarkers such as CA19-9.
Interventions
DIAGNOSTIC_TESTEXELiM assay (qRT-PCR validation)
Quantitative reverse-transcription PCR (qRT-PCR)-based validation assay performed on preoperative plasma samples from PDAC patients in the training and validation cohorts. Candidate microRNAs identified by small RNA sequencing were tested using the EXELiM assay to validate their predictive accuracy for occult liver metastasis detection prior to surgery.
DIAGNOSTIC_TESTEXELiM small RNA sequencing
High-throughput small RNA sequencing performed on preoperative plasma samples from PDAC patients in the discovery cohort to identify exosome-derived microRNAs associated with occult liver metastasis or early postoperative hepatic recurrence.
Sponsors
City of Hope Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed pancreatic ductal adenocarcinoma (PDAC) * Undergoing curative-intent pancreatectomy * Availability of preoperative plasma samples * Complete clinical and follow-up data * Written informed consent obtained
Exclusion criteria
* Synchronous or secondary malignancies * Non-adenocarcinoma histology * Lack of informed consent * Incomplete plasma sample data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Specificity | Through study completion, an average of 3 year | True Negative Rate: probability of a negative test result conditioned on absence of early liver metastasis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity | Through study completion, an average of 3 year | True Positive Rate: probability of a positive test result conditioned on the presence of early liver metastasis |
| Area Under the Receiver Operating Characteristic Curve (AUC) | Through study completion, an average of 3 year | Description: AUC representing the overall discriminative ability of the circRNA-based model. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAjay Goel, PhD
City of Hope Medical Center
Outcome results
None listed