Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is increasingly diagnosed in younger populations. Conventional biopsy techniques can be invasive and may not accurately capture tumor heterogeneity. Liquid biopsy, analyzing circulating tumor DNA (ctDNA), offers a minimally invasive and dynamic alternative for detecting genetic alterations critical to early diagnosis and personalized treatment strategies. Methods: We analyzed serum-derived ctDNA from 20 HCC patients to identify genetic variants using next-generation sequencing (NGS). Mutations in key oncogenes and tumor suppressor genes (eg, KIT, FGFR1, FGFR3, EGFR, BRAF, FBXW7) were evaluated for their association with clinical outcomes, including tumor size, metastasis, and overall survival. Statistical analyses were performed using SPSS (v.30), with survival curves assessed via the Kaplan-Meier method. Results: Of the 20 patients (mean age 64.8± 13.1 years), 35% had detectable ctDNA mutations. The most frequently observed alterations were in KIT (28.6% of ctDNA-positive patients), followed by FGFR1, FGFR3, EGFR, BRAF, and FBXW7. Patients harboring FGFR1 and FGFR3 mutations exhibited the poorest survival (3 and 7 months, respectively). Conversely, one patient with a BRAF mutation showed prolonged survival (60 months), and KIT mutations were linked to comparatively better outcomes. Overall, ctDNA-positive patients demonstrated shorter mean survival (22.5 months) than ctDNA-negative patients (35.7 months). Conclusion: Liquid biopsy-detected genetic alterations correlate with clinical outcomes in HCC, underscoring the prognostic value of ctDNA analysis. Mutations in FGFR1 and FGFR3 were associated with aggressive disease, suggesting these pathways as potential therapeutic targets. Integrating liquid biopsy with other diagnostic modalities may enhance personalized management and improve prognosis for patients with HCC. Plain Language Summary: Hepatocellular carcinoma (HCC) is a serious type of liver cancer that affects thousands of people each year. Detecting and treating it early can be difficult. Traditional tests often require taking tissue samples, which can be uncomfortable and risky for the patient. Our study looked at a blood-based test called a "liquid biopsy". Liquid biopsy tests for tiny fragments of cancer DNA (called circulating tumor DNA) in the bloodstream. We wanted to see if certain changes in this DNA might predict whether a patient's cancer could grow or spread. We analyzed blood samples from 20 people with HCC. We found that some had specific genetic changes, especially in genes called FGFR1 and FGFR3. People with these changes had a shorter life expectancy compared to those without them. On the other hand, different genetic changes in the BRAF and KIT genes were linked to longer survival. These findings suggest that liquid biopsy could help doctors identify patients who are at higher risk and may need more aggressive treatment. It may also help in choosing targeted therapies to block specific genetic changes. Overall, using liquid biopsy could lead to better and more personalized ways of treating liver cancer, with fewer side effects than traditional methods. Keywords: hepatocellular carcinoma, liquid biopsy, genetic alterations, next-generation sequencing, prognosis
Sarıtaş et al. (Mon,) studied this question.