![]() ![]() We then determined whether these genes could reliably identify MRD and predict early relapse in postoperative patients with HCC. In this study, we first performed a plasma-only ctDNA assay integrating genomic signatures to identify gene candidates associated with MRD in two cohorts. However, few studies have examined whether a plasma-only ctDNA assay can identify MRD in HCC with clinically meaningful specificity and sensitivity. Excitingly, one recent study reported that plasma-only MRD detection presented favorable sensitivity and specificity for predicting recurrence in colorectal cancer patients undergoing curative-intent surgery, comparable to the tumor-informed approach ( 30). Given the attractive advantages and redeemable disadvantages, this approach has increasingly been investigated in multiple solid tumors. The method’s drawback is the lack of sensitivity, which can be improved by incorporating serial longitudinal surveillance samples and examining a variety of biomarkers, such as ctDNA mutation and ctDNA methylation. The tumor-agnostic approach only requires plasma cfDNA sequencing with a fixed panel, which endows it with the advantages of noninvasiveness, convenience, cost-effectiveness, and rapid turnaround time. Additionally, designing individualized next-generation sequencing (NGS) panels also lengthens the turnaround time versus the fixed NGS panel. A potential limitation is that tumor heterogeneity in both space and time can affect its performance and might generate some false negative results ( 28, 29). The tumor-informed approach relies on tumor tissue sequencing to identify tumor-derived alterations for the design of patient-specific targeted gene panels for ctDNA tracking, which has presented effectiveness for monitoring MRD in some solid tumors after curative-intent treatment, including colon, lung, and pancreas cancer ( 24– 27). Currently, there are two available ctDNA detection strategies for monitoring MRD: tumor-informed and tumor-uninformed (also referred to as tumor-agnostic, tumor-naïve, or plasma-only) assay. ![]() There has been strong evidence that postoperative tumor-derived cfDNA (ctDNA) detection is correlated with MRD and could identify patients at high risk of relapse ( 20– 23). ![]() As a result, improving current therapeutic strategies and preventing recurrence might be achieved by establishing more precise MRD detection approaches.Ĭirculating cell-free DNA (cfDNA) is extracellular nucleic acid fragments released into the bloodstream due to apoptosis and necrosis from both healthy and malignant cells. Current postoperative surveillance methods are not sensitive or specific enough to detect MRD, such as monitoring clinical symptoms, tumor markers, and routine imaging. Consequently, there has been much interest in detecting and eliminating MRD to prevent relapse or for early treatment of degeneration. Early relapse has been reported to account for over 60% of all relapsed HCC events ( 9, 15– 19). Relapse in multiple solid tumors, including HCC, can be divided into early relapse (≤2 years) mainly caused by minimal residual disease (MRD) following resection, and late relapse (>2 years) caused by de novo tumors arising in a microenvironment predisposed to carcinogenesis ( 9– 14). Although hepatectomy is a widely accepted treatment option for HCC patients with good liver function, the relapse rate of up to 60%-70% within 5 years after surgery remains a severe problem ( 6– 8). Hepatocellular carcinoma (HCC) is the main type of primary liver cancer, comprising approximately 90% of patients. Over a million people per year are expected to be liver cancer patients by 2025 ( 5). Liver cancer is the second leading cause of cancer death, and its incidence is growing worldwide ( 1– 4). ![]()
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