An Exosomal microRNA Signature for Preoperative Staging in Colon Cancer

Официальное название

Machine Learning-Based Exosomal microRNA Signature for Preoperative Staging and Chemotherapy Eligibility in Colon Cancer

Обзор

Recent studies have highlighted the potential benefits of neoadjuvant chemotherapy (NAC) in colon cancer; however, its indication is generally limited to cases corresponding to pathological stage IIB or higher. Accurately identifying such high-risk cases before surgery remains challenging using conventional clinical diagnostics alone. Therefore, we hypothesized that integrating molecular biomarkers with preoperative clinical assessment could provide a more precise and sensitive evaluation of tumor aggressiveness. In this context, we focused on exosomal microRNAs, which are actively secreted from tumor cells and remain stable in circulation, and aimed to develop a machine learning-based biomarker panel. To achieve this, we initiated a multicenter study utilizing preoperative plasma samples to establish a reliable biomarker model for risk stratification and treatment decision-making in colon cancer.

Подробное описание

Colon cancer remains one of the leading causes of cancer-related mortality worldwide, and despite advances in screening and surgical techniques, a substantial proportion of patients continue to experience disease recurrence after curative resection. For patients with pathological stage IIB or higher disease, adjuvant chemotherapy is routinely recommended due to their elevated recurrence risk. However, accurately identifying these biologically aggressive cases before surgery remains a major clinical challenge, as current imaging-based staging often underestimates tumor burden and fails to capture underlying malignant potential. This diagnostic gap has hindered the optimal implementation of neoadjuvant chemotherapy (NAC) in colon cancer.

To address this issue, the investigators established the EXPOSE study (Exosomal microRNA Signature for Pre-Operative Stage and Eligibility Evaluation), a multicenter translational research initiative aiming to develop and validate a noninvasive, biologically informed diagnostic assay capable of identifying patients with high-risk colon cancer-equivalent to pathological stage IIB or higher-who may benefit from NAC.

The EXPOSE study will proceed through three structured phases.

1. In the discovery phase, exosomal microRNAs will be profiled using comprehensive small RNA sequencing to identify key biomarkers reflecting tumor aggressiveness. 2. In the training phase, the investigators will quantify candidate microRNAs using RT-qPCR and integrate their expression patterns via machine-learning algorithms to construct a predictive model for high-risk disease. 3. Finally, in the validation phase, the model's reproducibility, diagnostic accuracy, and generalizability will be tested in an independent clinical cohort.

The final EXPOSE assay is expected to serve as a liquid biopsy-based tool for preoperative staging, enabling more precise identification of biologically advanced colon cancer cases. Upon completion, this study will deliver a rigorously validated diagnostic model that combines molecular and clinical data to guide neoadjuvant treatment decisions and enhance personalized care in colon cancer management.

Вмешательства

• Диагностический тест Diagnostic Test: EXPOSE assay（Small RNA-seq of exosomal miRNAs）
  Candidates identified from small RNA sequencing
• Диагностический тест Diagnostic Test: EXPOSE RT-qPCR panel
  Quantification of exosomal microRNAs (RT-qPCR)

Первичные конечные точки

• Pathological Stage IIB or higher patients [Срок оценки: At time of pathology (1year after surgery)]

Вторичные конечные точки (2)

• Recurrence-Free Survival (RFS) [Срок оценки: Up to 120 months]
• Overall survival (OS) [Срок оценки: Up to 120 months]

Критерии участия

Критерии включения

• Pathologically confirmed colon cancer (Stage I-IV, UICC TNM 8th edition)
• Underwent curative-intent resection (with or without perioperative therapy)
• Preoperative plasma (or serum) samples available
• Clinical and prognostic data available

Критерии исключения

• No written informed consent
• Missing preoperative blood samples
• Missing survival/recurrence data
• Duplicate cases
• Non-adenocarcinoma histology

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• City of Hope Medical Center — Duarte

Публикации

• Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, Vignat J, Ferlay J, Murphy N, Bray F. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023 Feb;72(2):338-344. doi: 10.1136/gutjnl-2022-327736. Epub 2022 Sep 8. PMID 36604116
• Cardoso R, Guo F, Heisser T, Hackl M, Ihle P, De Schutter H, Van Damme N, Valerianova Z, Atanasov T, Majek O, Muzik J, Nilbert MC, Tybjerg AJ, Innos K, Magi M, Malila N, Bouvier AM, Bouvier V, Launoy G, Woronoff AS, Cariou M, Robaszkiewicz M, Delafosse P, Poncet F, Katalinic A, Walsh PM, Senore C, Rosso S, Vincerzevskiene I, Lemmens VEPP, Elferink MAG, Johannesen TB, Korner H, Pfeffer F, Bento MJ, PMID 34048685
• Taieb J, Svrcek M, Cohen R, Basile D, Tougeron D, Phelip JM. Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment. Eur J Cancer. 2022 Nov;175:136-157. doi: 10.1016/j.ejca.2022.07.020. Epub 2022 Sep 14. PMID 36115290
• Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17. PMID 38230766
• Burley N, Lee Y, Liu L, Gangi A, Nasseri Y, Atkins K, Zaghiyan K, Murrell Z, Osipov A, Hendifar A, Hitchins M, Gong J. ctDNA-guided adjuvant immunotherapy in colorectal cancer. Immunotherapy. 2024;16(20-22):1197-1202. doi: 10.1080/1750743X.2024.2430941. Epub 2024 Nov 17. PMID 39552190
• Tan PB, Verschoor YL, van den Berg JG, Balduzzi S, Kok NFM, Ijsselsteijn ME, Moore K, Jurdi A, Tin A, Kaptein P, van Leerdam ME, Haanen JBAG, Voest EE, de Miranda NFCC, Schumacher TN, Wessels LFA, Chalabi M. Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers. Nature. 2025 Dec;648(8094):726-735. doi: 10.1038/s41586-025-09679-4. Epub 2025 Oct 20. PMID 41115454
• Krsul D, Prenc E, Pozgaj L, Stefok D, Pongrac P, Podolski M, Radicevic AP, Karlovic D, Jerkovic A, Golcic M, Drazic I, Glavas Krsul S, Fuckar Cupic D, Erakovic Haber V, Zelic M. Diagnostic Relevance of miR-185, miR-141, and miR-21 in Colon Carcinoma: Insights into Tumor Sidedness and Reference Gene Selection. Biomedicines. 2025 Oct 10;13(10):2460. doi: 10.3390/biomedicines13102460. PMID 41153743
• Serafin M, Maka M, Szostek J, Kania I, Jablonska B, Mrowiec S. Side-Specific Prognostic Factors in Colon Cancer: A Retrospective Analysis of Right- and Left-Sided Tumors. Cancers (Basel). 2025 Oct 14;17(20):3315. doi: 10.3390/cancers17203315. PMID 41154372

Идентификаторы

NCT: NCT07255729 · 23228/EXPOSE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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