An Exosome-Based Liquid Biopsy for the Differential Diagnosis of Primary Liver Cancer

Обзор

It is sometimes difficult to precisely understand whether a primary liver cancer is a hepatocellular carcinoma or a cholangiocarcinoma. The researchers will develop and validate a liquid biopsy, based on exosomal content analysis and powered by machine learning, to help clinicians differentiate these two cancers before surgery.

Подробное описание

Primary liver cancers (PLCs) encompass a diverse group of malignancies originating from the liver, collectively ranking as the third leading cause of cancer-related mortality worldwide in 2020. Among PLCs, intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) represent the most predominant subtypes. Despite their collective grouping as PLCs, ICC and HCC patients exhibit distinct etiologies, pathologies, and clinical characteristics, necessitating different treatment approaches. Accurate differentiation between ICC and HCC is paramount to optimize patient outcomes and guide personalized treatment decisions. However, a definitive diagnosis is often obtained only after the pathological review of the resected neoplastic tissue, which requires invasive tumor sampling and poses risks of complications such as hemorrhage and tumor cell seeding. Consequently, there is a pressing clinical need to develop noninvasive diagnostic approaches to achieve an accurate differential diagnosis for patients with these distinct forms of PLCs.

This study involves the development and validation of a liquid biopsy, assessing circulating exosomal microRNAs (exo-miRNA) for indirect sampling of tumor tissue in the bloodstream. The researchers intend to harness machine learning and bioinformatics to create a cost-efficient, non-invasive, clinic-friendly assay with high sensitivity and specificity, aiding the differential diagnosis between ICC and HCC.

The researchers intend to do so in three phases:

1. To perform comprehensive small RNA-Seq from exo-miRNA from patients with ICC and HCC. 2. To develop and train a differential diagnosis panel based on advanced machine-learning models to obtain a final differential diagnosis biomarker. 3. To validate the findings in an independent cohort of ICC and HCC.

In summary, this proposal promises to improve patient care and help clinicians perform a more reliable differential diagnosis between ICC and HCC in patients with primary liver cancer.

Вмешательства

• Диагностический тест ELUCIDATE
  ELUCIDATE (Evaluation of Liver Cholangiocarcinoma Intrahepatic)

Первичные конечные точки

• Sensitivity [Срок оценки: Through study completion, an average of 1 year]

Вторичные конечные точки (2)

• Specificity [Срок оценки: Through study completion, an average of 1 year]
• Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy) [Срок оценки: Through study completion, an average of 1 year]

Критерии участия

Критерии включения

• A histologically confirmed diagnosis of hepatocellular carcinoma
• A histologically confirmed diagnosis of intrahepatic cholangiocarcinoma
• Received standard diagnostic and staging procedures as per local guidelines
• Availability of at least one blood-derived sample, drawn before receiving any curative-intent treatment

Критерии исключения

• Lack of or inability to provide informed consent
• Synchronous hepatocellular carcinoma and intrahepatic cholangiocarcinoma
• Primary liver cancer other than hepatocellular carcinoma or intrahepatic cholangiocarcinoma
• Secondary liver cancer

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Только случаи

Центры проведения

Япония · 4 центра

• Graduate School of Medical Sciences, Kyushu University — Fukuoka
• Graduate School of Medical Sciences, Kumamoto University — Kumamoto
• Hokkaido University Graduate School of Medicine — Sapporo
• Tokushima University — Tokushima

США · 1 центр

• City of Hope Medical Center — Duarte

Публикации

• Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, Roberts LR, Heimbach JK. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018 Aug;68(2):723-750. doi: 10.1002/hep.29913. No abstract available. PMID 29624699
• Wu Y, Xia C, Chen J, Qin Q, Ye Z, Song B. Diagnostic performance of magnetic resonance imaging and contrast-enhanced ultrasound in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma: a meta-analysis. Abdom Radiol (NY). 2024 Jan;49(1):34-48. doi: 10.1007/s00261-023-04064-z. Epub 2023 Oct 12. PMID 37823913
• El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008 May;134(6):1752-63. doi: 10.1053/j.gastro.2008.02.090. PMID 18471552
• Vigano L, Lleo A, Muglia R, Gennaro N, Sama L, Colapietro F, Roncalli M, Aghemo A, Chiti A, Di Tommaso L, Solbiati L, Colombo M, Torzilli G. Intrahepatic cholangiocellular carcinoma with radiological enhancement patterns mimicking hepatocellular carcinoma. Updates Surg. 2020 Jun;72(2):413-421. doi: 10.1007/s13304-020-00750-5. Epub 2020 Apr 22. PMID 32323164
• Kovac JD, Jankovic A, Dikic-Rom A, Grubor N, Antic A, Dugalic V. Imaging Spectrum of Intrahepatic Mass-Forming Cholangiocarcinoma and Its Mimickers: How to Differentiate Them Using MRI. Curr Oncol. 2022 Jan 30;29(2):698-723. doi: 10.3390/curroncol29020061. PMID 35200560
• Arbelaiz A, Azkargorta M, Krawczyk M, Santos-Laso A, Lapitz A, Perugorria MJ, Erice O, Gonzalez E, Jimenez-Aguero R, Lacasta A, Ibarra C, Sanchez-Campos A, Jimeno JP, Lammert F, Milkiewicz P, Marzioni M, Macias RIR, Marin JJG, Patel T, Gores GJ, Martinez I, Elortza F, Falcon-Perez JM, Bujanda L, Banales JM. Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis PMID 28555885
• Banales JM, Inarrairaegui M, Arbelaiz A, Milkiewicz P, Muntane J, Munoz-Bellvis L, La Casta A, Gonzalez LM, Arretxe E, Alonso C, Martinez-Arranz I, Lapitz A, Santos-Laso A, Avila MA, Martinez-Chantar ML, Bujanda L, Marin JJG, Sangro B, Macias RIR. Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis. Hepatology. 2019 Aug;70 PMID 30325540
• Huang C, Xu X, Wang M, Xiao X, Cheng C, Ji J, Fang M, Gao C. Serum N-glycan fingerprint helps to discriminate intrahepatic cholangiocarcinoma from hepatocellular carcinoma. Electrophoresis. 2021 Jun;42(11):1187-1195. doi: 10.1002/elps.202000392. Epub 2021 Mar 1. PMID 33570803

Идентификаторы

NCT: NCT06342414 · 23228/ELUCIDATE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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