What question did this study set out to answer?

The aim is to assess the effectiveness of liquid biopsy methods, specifically ctDNA and exosomal microRNA, in predicting outcomes for patients with resectable perihilar cholangiocarcinoma.

April 4, 2026Open Access

139P Clinical performance of novel exosomal liquid RNA biopsy assay in lung cancer segment

Key Points

The aim is to assess the effectiveness of liquid biopsy methods, specifically ctDNA and exosomal microRNA, in predicting outcomes for patients with resectable perihilar cholangiocarcinoma.
Prospective enrollment of 18 patients with resectable perihilar cholangiocarcinoma.
Collection of plasma samples preoperatively, postoperatively, and during adjuvant chemotherapy.
Quantification of ctDNA using droplet digital polymerase chain reaction (ddPCR).
Isolation of exosomes and analysis of microRNA profiles through sequencing.
Correlation of liquid biopsy parameters with disease-free survival (DFS).
KRAS codon 12 mutations were the most common alterations found.
Patients who remained ctDNA-negative had significantly longer DFS (hazard ratio 6.7).
Patients who converted to ctDNA positivity during treatment had poorer DFS (hazard ratio 5.8).
Higher preoperative ctDNA mutation burden correlated with worse outcomes.
Exosomal microRNA profiles showed limited prognostic value compared to ctDNA.

Abstract

Background: Surgery is the only potentially curative treatment for resectable perihilar cholangiocarcinoma; however, recurrence rates remain high and prognosis is poor.Although adjuvant systemic chemotherapy is routinely administered, reliable biomarkers to guide perioperative treatment decisions are lacking.Liquid biopsy approaches may enable dynamic assessment of molecular residual disease and help optimize treatment strategies.Methods: Between February 2022 and March 2025, 18 patients with resectable perihilar cholangiocarcinoma were prospectively enrolled.Plasma samples were collected preoperatively, postoperatively before adjuvant chemotherapy, and during adjuvant treatment.Circulating tumor DNA (ctDNA) was quantified using droplet digital polymerase chain reaction (ddPCR).Exosomes were isolated using a standardized workflow, and exosomal microRNA profiles were analysed by microRNA sequencing.KRAS, BRAF and IDH genes were screened, and mutation burden was calculated for each patient.Liquid biopsy parameters were correlated with diseasefree survival (DFS).Results: KRAS codon 12 mutations represented the most frequent genetic alteration.Analysis of ctDNA dynamics demonstrated that patients who remained serially ctDNA-negative had significantly longer DFS compared with patients with persistent ctDNA positivity (hazard ratio HR 6.7; p < 0.001) or those who converted to ctDNA positivity during adjuvant therapy (HR 5.8; p < 0.001).In contrast, exosomal microRNA profiles showed limited prognostic discrimination.Higher preoperative ctDNA mutation burden was associated with inferior outcomes under adjuvant therapy.During follow-up, four patients died. Conclusions:In resectable perihilar cholangiocarcinoma, perioperative ctDNA dynamics outperform exosomal microRNAs in risk stratification during adjuvant chemotherapy.Preoperative and longitudinal ctDNA assessment may support personalized perioperative treatment strategies, including identification of patients who may benefit from alternative approaches such as neoadjuvant therapy.

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