Liquid Biopsy Using Exosomal miRNA Enables Risk Stratification of Potential Metastasis in Patients With Intrahepatic Cholangiocarcinoma.

NCT07224737 | Completed

• 1 other identifier: 23228/EXOMIC
• Study Type: observational
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

Occult metastasis at the time of surgery is a major driver of poor outcomes in intrahepatic cholangiocarcinoma (ICC), yet reliable preoperative biomarkers to identify such patients are lacking. The EXOMIC study aims to develop and validate a circulating exosomal microRNA (exo-miRNA)-based liquid biopsy assay to detect occult metastasis preoperatively in patients with resectable ICC.

Conditions

Intrahepatic Cholangiocarcinoma (Icc)

Keywords

Exosomal miRNA; ICC; Liquid Biopsy; Occult metastasis; Tumor recurrence; Liver cancer

Outcome Measures

Primary Outcomes (1)

• Recurrence Free Survival

  The time period from surgery to recurrence of ICC.

  3 years

Secondary Outcomes (1)

• Overall Survival

  5 years

Study Arms (6)

Training Cohort - ICC with Occult Metastasis

The cohort of ICC patients who had occult metastasis detected at the time of surgery. Preoperative samples were analyzed using the EXOMIC qRT-PCR assay to validate candidate exosomal microRNAs identified in the discovery cohort.

Diagnostic Test: EXOMIC assay (qRT-PCR validation)

Training Cohort - ICC without Occult Metastasis

The cohort of ICC patients without occult metastasis at the time of surgery. Preoperative samples were analyzed with the EXOMIC qRT-PCR assay to evaluate differential miRNA expression and refine the predictive model for occult metastasis detection.

Diagnostic Test: EXOMIC assay (qRT-PCR validation)

Validation Cohort - ICC with Occult Metastasis

The cohort of ICC patients with occult metastasis at the time of primary tumor resection. The EXOMIC qRT-PCR assay was applied to confirm the predictive value of the exosomal miRNA panel in identifying occult metastasis prior to surgery.

Diagnostic Test: EXOMIC assay (qRT-PCR validation)

Validation Cohort - ICC without Occult Metastasis

The cohort of ICC patients without occult metastasis at the time of surgery. Preoperative samples were analyzed with the EXOMIC qRT-PCR assay to evaluate differential miRNA expression and refine the predictive model for occult metastasis detection.

Diagnostic Test: EXOMIC assay (qRT-PCR validation)

Discovery Cohort - ICC with Occult Metastasis

Patients with intrahepatic cholangiocarcinoma (ICC) who were found to have occult metastasis at the time of primary tumor resection in the discovery cohort. Preoperative samples were analyzed using small RNA sequencing to identify exosome-derived microRNAs associated with the presence of occult metastasis.

Diagnostic Test: EXOMIC small RNA sequencing

Discovery Cohort - ICC without Occult Metastasis

Patients with ICC who had no occult metastasis at the time of primary tumor resection in the discovery cohort. Preoperative samples from these patients were analyzed by small RNA sequencing and compared with those from patients with occult metastasis to identify candidate microRNAs.

Diagnostic Test: EXOMIC small RNA sequencing

Interventions

EXOMIC small RNA sequencing DIAGNOSTIC_TEST

High-throughput small RNA sequencing performed on preoperative serum or plasma samples from patients with intrahepatic cholangiocarcinoma (ICC) to identify exosome-derived microRNAs associated with occult metastasis at the time of surgery. Sequencing data were analyzed to detect differentially expressed miRNAs between patients with and without occult metastasis in the discovery cohort.

Discovery Cohort - ICC with Occult Metastasis; Discovery Cohort - ICC without Occult Metastasis

EXOMIC assay (qRT-PCR validation) DIAGNOSTIC_TEST

Quantitative reverse transcription PCR (qRT-PCR)-based validation of candidate exosomal microRNAs identified through small RNA sequencing. This assay was performed on preoperative serum or plasma samples from independent ICC patient cohorts to validate the predictive value of selected miRNAs for occult metastasis detection prior to surgical resection.

Training Cohort - ICC with Occult Metastasis; Training Cohort - ICC without Occult Metastasis; Validation Cohort - ICC with Occult Metastasis; Validation Cohort - ICC without Occult Metastasis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

250

You may qualify if:

• Histologically confirmed ICC (clinical stage I-III).
• Undergoing curative-intent hepatectomy.
• Availability of preoperative pasma or serum sample (≥200 µL).
• Standard staging imaging completed per institutional protocol.
• Written informed consent.

You may not qualify if:

• Extrahepatic cholangiocarcinoma or gallbladder cancer.
• Synchronous non-ICC malignancy.
• Inadequate clinical follow-up.
• Inability to consent.

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91016, United States

Location

Related Publications (13)

• Huang G, Zhang H, Yang Z, Li Q, Yuan H, Chen P, Xie C, Meng B, Zhang X, Chen K, Yu H. Predictive value of HTS grade in patients with intrahepatic cholangiocarcinoma undergoing radical resection: a multicenter study from China. World J Surg Oncol. 2024 Jan 11;22(1):17. doi: 10.1186/s12957-023-03281-6.

  PMID: 38200585 BACKGROUND

• Swanson K, Wu E, Zhang A, Alizadeh AA, Zou J. From patterns to patients: Advances in clinical machine learning for cancer diagnosis, prognosis, and treatment. Cell. 2023 Apr 13;186(8):1772-1791. doi: 10.1016/j.cell.2023.01.035. Epub 2023 Mar 10.

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• Kojima T, Umeda Y, Fuji T, Niguma T, Sato D, Endo Y, Sui K, Inagaki M, Oishi M, Ota T, Hioki K, Matsuda T, Aoki H, Hirai R, Kimura M, Yagi T, Fujiwara T. Efficacy of surgical management for recurrent intrahepatic cholangiocarcinoma: A multi-institutional study by the Okayama Study Group of HBP surgery. PLoS One. 2020 Sep 3;15(9):e0238392. doi: 10.1371/journal.pone.0238392. eCollection 2020.

  PMID: 32881910 BACKGROUND

• Feng J, Liang B, Zhang HY, Liu Z, Jiang K, Zhao XQ. Prognostic factors for patients with mass-forming intrahepatic cholangiocarcinoma: A case series of 68 patients. World J Gastrointest Surg. 2022 May 27;14(5):442-451. doi: 10.4240/wjgs.v14.i5.442.

  PMID: 35734620 BACKGROUND

• Doussot A, Gonen M, Wiggers JK, Groot-Koerkamp B, DeMatteo RP, Fuks D, Allen PJ, Farges O, Kingham TP, Regimbeau JM, D'Angelica MI, Azoulay D, Jarnagin WR. Recurrence Patterns and Disease-Free Survival after Resection of Intrahepatic Cholangiocarcinoma: Preoperative and Postoperative Prognostic Models. J Am Coll Surg. 2016 Sep;223(3):493-505.e2. doi: 10.1016/j.jamcollsurg.2016.05.019. Epub 2016 Jun 11.

  PMID: 27296525 BACKGROUND

• Yu TH, Chen X, Zhang XH, Zhang EC, Sun CX. Clinicopathological characteristics and prognostic factors for intrahepatic cholangiocarcinoma: a population-based study. Sci Rep. 2021 Feb 17;11(1):3990. doi: 10.1038/s41598-021-83149-5.

  PMID: 33597569 BACKGROUND

• Clements O, Eliahoo J, Kim JU, Taylor-Robinson SD, Khan SA. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: A systematic review and meta-analysis. J Hepatol. 2020 Jan;72(1):95-103. doi: 10.1016/j.jhep.2019.09.007. Epub 2019 Sep 16.

  PMID: 31536748 BACKGROUND

• Bertuccio P, Malvezzi M, Carioli G, Hashim D, Boffetta P, El-Serag HB, La Vecchia C, Negri E. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019 Jul;71(1):104-114. doi: 10.1016/j.jhep.2019.03.013. Epub 2019 Mar 23.

  PMID: 30910538 BACKGROUND

• An L, Zheng R, Zhang S, Chen R, Wang S, Sun K, Lu L, Zhang X, Zhao H, Zeng H, Wei W, He J. Hepatocellular carcinoma and intrahepatic cholangiocarcinoma incidence between 2006 and 2015 in China: estimates based on data from 188 population-based cancer registries. Hepatobiliary Surg Nutr. 2023 Feb 28;12(1):45-55. doi: 10.21037/hbsn-21-75. Epub 2021 Jul 21.

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• Fiste O, Ntanasis-Stathopoulos I, Gavriatopoulou M, Liontos M, Koutsoukos K, Dimopoulos MA, Zagouri F. The Emerging Role of Immunotherapy in Intrahepatic Cholangiocarcinoma. Vaccines (Basel). 2021 Apr 22;9(5):422. doi: 10.3390/vaccines9050422.

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  PMID: 40446770 BACKGROUND

• Zhao B, Cheng Q, Cao H, Zhou X, Li T, Dong L, Wang W. Dynamic change of serum CA19-9 levels in benign and malignant patients with obstructive jaundice after biliary drainage and new correction formulas. BMC Cancer. 2021 May 7;21(1):517. doi: 10.1186/s12885-021-08204-w.

  PMID: 33962560 BACKGROUND

MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension; Recurrence; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Ajay Goel, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 5, 2025
• Study Start: June 21, 2024
• Primary Completion: January 18, 2026
• Study Completion: February 18, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)