KEY TAKEAWAYS
- The PRIMe-liver trial aimed to develop and evaluate convenient, affordable, and highly sensitive tools for early PLC detection in LC and CHVI pts.
- COMET’s promising combination of low cost and high accuracy makes it a strong candidate for early PLC detection in LC and CHVI pts, although further prospective validation is necessary for confirmation.
Detecting primary liver cancer (PLC) in individuals with liver cirrhosis (LC) or chronic hepatitis virus infection (CHVI) at an early stage has been shown to enhance survival rates significantly.
Herein, Tian Yang and other researchers aimed to develop convenient and affordable tools with high sensitivity for the early detection of PLC in LC/CHVI patients (pts), aiming to improve survival through timely diagnosis.
In the observational study, tissue and plasma samples from precisely 159 healthy individuals and 89 pts diagnosed with PLC, LC, or CHVI underwent sequencing via a targeted methylation panel, including approximately 70,000 CpGs. The objective was to identify candidate methylated DNA markers (MDMs).
In phase I, the performance of each chosen MDM was validated using 175 plasma samples (PLC: n=101; LC/CHVI: n=74) through the CO-methylation amplification real-time PCR (COMET) assay. Subsequently, a logistic model was trained and validated in Phase II using 310 plasma samples (HCC: n=212; cHCC-CC: n=12; CHVI: n=106), maintaining a training-to-validation ratio 2:1.
The result showed that the 11 selected MDMs consistently demonstrated statistically significant differences in tissue samples between PLC and LC/CHVI and in plasma samples between PLC and LC/CHVI (P<0.05).
In Phase I, 8 out of the 11 MDMs were further investigated, with an Area Under the Curve (AUC) exceeding 0.80 for distinguishing PLC and LC/CHVI. In Phase II, the MDM-based model achieved a sensitivity of 87.2% (95% CI, 80.8%–92.4%) and 88.0% (78.4%–94.4%), with respective specificity values of 97.1% (90.1%–99.7%) and 100% (90.3%–100%) in the training and validation sets.
In the validation set, sensitivity for pts with BCLC stage 0, diameter<3 cm, AFP-negative, and PIVKA-II-negative was 90.0% (55.5%–99.7%), 88.9% (65.3%–98.6%), 80.6% (64.0%–91.8%), and 81.3% (54.4%–96.0%), respectively. The model detected 19 out of 24 cases of intrahepatic cholangiocarcinoma, achieving a sensitivity of 79.3% (57.8%–92.9%). By combining AFP and PIVKA-II, the model demonstrated an increased sensitivity of 93.3% (85.1%–97.8%) and a specificity of 100.0% (90.3%–100%).
The study showed that the COMET, distinguished by its cost-effectiveness and commendable accuracy, manifests a promising capability for detecting PLC among individuals with concurrent LC or CHVI. Subsequent validation within a prospective cohort is imperative to fortify its credibility and applicability in clinical settings.
This study is sponsored by The First Hospital of Jilin University
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/78
Clinical Trial: https://clinicaltrials.gov/study/NCT05996666
Yang T, Wang N, Zhu X, et al.” Effective identification of primary liver cancer from cirrhosis or chronic hepatitis virus infection using eight methylated plasma DNA markers: Marker discovery, phase I pilot, and phase II clinical validation.” Presented at ESMO Asia Congress 2023. (Abstract: 621P).
