Sarıtaş Ahmet Gökhan, Yavuz Burak, Aydın İshak, Ağca Harun, Topal Uğur, Ballı Tuğsan, Bisgin Atil, Ülkü Abdullah, Akçam Atılgan Tolga
Cukurova University Faculty of Medicine, Department of General Surgery, Adana, Turkey.
Çukurova University Faculty of Medicine, Department of Radiology, Adana, Turkey.
J Hepatocell Carcinoma. 2025 Sep 5;12:2035-2043. doi: 10.2147/JHC.S529189. eCollection 2025.
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.
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.
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).
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.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因，且在年轻人群中的诊断率越来越高。传统活检技术具有侵入性，可能无法准确捕捉肿瘤异质性。液体活检通过分析循环肿瘤DNA（ctDNA），为检测对早期诊断和个性化治疗策略至关重要的基因改变提供了一种微创且动态的替代方法。
我们使用下一代测序（NGS）分析了20例HCC患者血清来源的ctDNA，以鉴定基因变异。评估关键癌基因和肿瘤抑制基因（如KIT、FGFR1、FGFR3、EGFR、BRAF、FBXW7）的突变与临床结局的相关性，包括肿瘤大小、转移和总生存期。使用SPSS（v.30）进行统计分析，通过Kaplan-Meier方法评估生存曲线。
在20例患者（平均年龄64.8±13.1岁）中，35%可检测到ctDNA突变。最常观察到的改变发生在KIT基因（ctDNA阳性患者中的28.6%），其次是FGFR1、FGFR3、EGFR、BRAF和FBXW7。携带FGFR1和FGFR3突变的患者生存期最短（分别为3个月和7个月）。相反，1例BRAF突变患者生存期延长（60个月），KIT突变与相对较好的结局相关。总体而言，ctDNA阳性患者的平均生存期（22.5个月）短于ctDNA阴性患者（35.7个月）。
液体活检检测到的基因改变与HCC的临床结局相关，强调了ctDNA分析的预后价值。FGFR1和FGFR3突变与侵袭性疾病相关，提示这些通路可能是潜在的治疗靶点。将液体活检与其他诊断方法相结合，可能会加强个性化管理并改善HCC患者的预后。
