PreCar Phase II Launches: Advancing cfDNA-Based Liquid Biopsy for Accurate Differentiation of Benign and Malignant Liver Nodules

On July 10, the PreCar project, the largest nationwide prospective study on liver cancer in China, was officially announced at the 14th National Academic Conference on Clinical Hepatology and the 4th Annual Meeting of the Huaxia Hepatology Alliance.Initiate Phase II，Led by Professor Ren Hong from the Second Affiliated Hospital of Chongqing Medical University, and involving nearly 20 top medical institutions across China, a nationwide multicenter study was conducted to focus on the differentiation between benign and malignant liver nodules.。

At the launch ceremony of the Phase II PreCar project, as the project leadProfessor Hong RenIt first emphasized the core objective of the Phase II study of the PreCar project, with the research team building upon the Phase I project.Using cfDNA Whole-Genome Sequencing to Aid Clinical Methods in Differentiating Benign and Malignant Liver Nodules, making it simpler and more feasible while improving the efficiency of differentiating between benign and malignant hepatic nodules in clinical practice.

Prof. Ren Hong’s On-Site Remarks

Professor Hong RenIt was also pointed out at the launch ceremony that the key to achieving the clinical goal of reducing the case fatality rate of viral hepatitis by 65% by 2030 lies in lowering the proportion of liver cancer caused by viral hepatitis. However, 70% of patients with hepatocellular carcinoma (HCC) are already diagnosed at intermediate or advanced stages, while less than 30% are detected early. Therefore, there is an urgent need to strengthen early screening for liver cancer in clinical practice. The Phase II of the PreCar project will introduce a new detection method—Using genetic diagnostics to differentiate between benign and malignant liver nodules: The project plans to enroll 1,000 patients with diagnostically challenging liver nodules to expand the validation of application scenarios for whole-genome sequencing of cell-free DNA (cfDNA)., contributing to the early clinical screening of liver cancer and facilitating its timely implementation.

Since its launch in 2018, the PreCar project has conducted a three-year prospective study focused on early screening and diagnosis of liver cancer, completing early-stage liver cancer screening for over 10,000 individuals. The first research findings from Phase I of the PreCar project have been published in Cell Research, demonstrating significantly higher sensitivity and specificity compared to other publicly available liver cancer detection technologies.

Phase II of the project was announced at the National Multi-center Prospective Study on Ultra-early Warning and Screening for Hepatocellular Carcinoma (PreCar) Progress Conference and the First Summit Forum on Precision Prevention and Control for Early Diagnosis and Treatment of Tumors, held on April 17 this year:The Phase II of the PreCar project will expand from early screening for liver cancer to comprehensive disease management, encompassing precise clinical screening, auxiliary early diagnosis of benign and malignant lesions, and dynamic monitoring of postoperative recurrence in liver cancer patients.。

From the exploratory Phase I to the in-depth Phase II of the PreCar project, few companies in the field of early cancer screening and diagnosis are willing to invest such significant effort and time to support frontier academic research on a specific cancer type. However, Berry Oncology, as the lead executing entity of the PreCar project, has achieved this, which is alsoThe Sole Third-Party Technical Support Provider Behind the PreCar ProjectAdhering to the principles of evidence-based medicine, the company validated the feasibility of its technical approach through an ultra-large-scale prospective cohort for early cancer screening, thereby laying a solid clinical data foundation for the launch of its liver cancer early screening product, “Laisining,” which was developed based on this project’s validation and brought to market in August 2020.

Clinically, most patients with liver disease follow the "hepatitis B–cirrhosis–liver cancer" progression pattern. Statistics indicate that 70% of primary liver cancer cases arise on the background of cirrhosis. Cirrhosis is typically characterized by numerous nodules of varying sizes, including regenerative nodules (RN) and dysplastic nodules (DN). Among these, high-grade dysplastic nodules (HGDN) can progress to hepatocellular carcinoma (HCC) through a "nodule-in-nodule" pattern. Research data show that patients with HGDN have a fourfold higher risk of progressing to HCC compared to those without HGDN; therefore, HGDN is often considered a precancerous lesion for HCC.

Accurate diagnosis of the benign or malignant nature of liver nodules has become a critical component in the treatment of liver cancer. However, clinical identification of liver nodules remains challenging. As the liver is a highly vascularized organ, the actual detection rate for differentiating benign from malignant nodules using conventional imaging and serological methods is relatively low. When necessary, liver needle biopsy based on pathological examination is required to confirm the diagnosis.

However, when pathological specimens of hepatic nodules are unavailable in clinical practice, imaging examinations—such as abdominal color Doppler ultrasound, contrast-enhanced ultrasound (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI)—become the primary methods for clinically diagnosing precancerous lesions of hepatocellular carcinoma. Nevertheless, imaging modalities have the following limitations in differentiating benign from malignant nodules: conventional ultrasound can only reflect morphological changes of the lesion and cannot provide a comprehensive analysis of the features of small hepatocellular carcinoma and atypical hepatocellular carcinoma; its sensitivity for detecting early-stage hepatocellular carcinoma is poor, at only 47%. Furthermore, for nodules lacking typical imaging characteristics, imaging examinations are even less capable of establishing a definitive diagnosis.

The Phase II PreCar project is expected to facilitate precise clinical differentiation between benign and malignant liver nodules. In previous PreCar studies, whole-genome sequencing (WGS) of cell-free DNA (cfDNA) was employed to analyze the genomic characteristics of cfDNA in healthy controls (CTRL), patients with liver cirrhosis (LC), and patients with hepatocellular carcinoma (HCC), thereby constructing an early screening model for hepatocellular carcinoma.It not only enables precise detection of very early-stage and early-stage hepatocellular carcinoma, but also demonstrates strong capability in differentiating between benign and malignant liver nodules.This highlights the potential of the technology. If cfDNA testing is utilized for the differential diagnosis of hepatic nodules, it can not only facilitate stratified screening of patients with high suspicion of malignancy but also improve the detection rate of liver cancer, thereby enabling precision diagnosis and treatment.

Thus, the Phase II PreCar project was launched. Building on the preliminary clinical studies of PreCar, researchers will employ cfDNA whole-genome sequencing (WGS) technology (Laisining), in combination with imaging, serological markers, and other clinical indicators,To Validate the Actual Clinical Application Value of Lesining in Differentiating Benign from Malignant Liver Nodules, with the aim of providing new tools for establishing optimal management strategies for liver nodules in the future, better meeting clinical diagnostic needs, promoting early diagnosis and treatment of liver cancer, and improving the five-year survival rate of liver cancer patients.

Laisining is a testing product independently developed by Berry Oncology, validated based on the PreCar project.. By detecting cfDNA in the peripheral blood of subjects, Lesion can analyze multi-dimensional variation information—including nucleosome footprints, fragment size distribution, end motifs, and copy number variations—across the whole genome. It applies a liver cancer risk warning model to comprehensively weight these multi-dimensional variation data to derive the HIFI score, thereby assessing the risk of liver cancer.

The prospective Phase II study of the PreCar project is expected to expand the clinical applications of Laisining, ranging from the detection of early-stage hepatocellular carcinoma to the differentiation between benign and malignant liver nodules. This also ensures that cutting-edge scientific research is supported by corresponding products, facilitating a true transition from research to clinical practice and benefiting countless liver cancer patients. Berry Oncology remains committed to technological exploration through prospective studies.Application Expansion from Point (Early Screening for Liver Cancer) to Surface (Full-Course Disease Management)In the future, it will also provide precise postoperative dynamic monitoring for liver cancer patients based on highly sensitive and specific cfDNA liquid biopsy technology, meeting the clinical need to assist in preventing the risk of liver cancer recurrence, which is equally promising.