Li Jin, Bai Ling, Xin Zhaodan, Song Jiajia, Chen Hao, Song Xingbo, Zhou Juan
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Med + Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China.
Sci Rep. 2025 Jan 29;15(1):3620. doi: 10.1038/s41598-025-87545-z.
Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, and ranks among the most lethal malignancies globally, primarily due to its high rates of recurrence and metastasis. Despite the urgency, no reliable biomarkers currently exist for predicting tumor recurrence in HCC. Telomerase reverse transcriptase (TERT) promoter mutations (TERTpm) and cellular tumor antigen p53 mutations (TP53m) have been frequently documented in HCC, but their combined clinical significance remains undefined. In this study, we investigated the clinical implications of TERTpm, TP53m, and their co-occurrence in 50 HCC tissue samples using the next-generation sequencing (NGS) technology. We identified TERTpm (C228T) and TP53m in 16 (32%) and 24 (48%) samples, respectively. Our findings indicate that these mutations are more prevalent in male patients (100% for TERTpm, 83.33% for TP53m), in those with solitary tumors (87.5% for both), in individuals with G2-G3 hepatitis (100% / 83.3%), and in cases of moderately differentiated tumors (75.0% / 83.3%). Furthermore, patients with both TERTpm and TP53m exhibited a significantly higher risk of tumor relapse (P < 0.05) and shorter progression-free survival (P < 0.05). Collectively, our results suggest that presence of both TERTpm and TP53m may serve as a robust predictor of tumor recurrence and a marker of poor prognosis in HCC.
肝细胞癌（HCC）是肝癌最常见的形式，在全球最致命的恶性肿瘤中名列前茅，主要原因是其高复发率和转移率。尽管情况紧急，但目前尚无可靠的生物标志物可用于预测HCC中的肿瘤复发。端粒酶逆转录酶（TERT）启动子突变（TERTpm）和细胞肿瘤抗原p53突变（TP53m）在HCC中经常被记录到，但其联合临床意义仍不明确。在本研究中，我们使用下一代测序（NGS）技术研究了TERTpm、TP53m及其同时出现情况在50例HCC组织样本中的临床意义。我们分别在16例（32%）和24例（48%）样本中鉴定出TERTpm（C228T）和TP53m。我们的研究结果表明，这些突变在男性患者中更常见（TERTpm为100%，TP53m为83.33%），在单发肿瘤患者中（两者均为87.5%），在G2 - G3级肝炎患者中（分别为100% / 83.3%），以及在中度分化肿瘤患者中（分别为75.0% / 83.3%）。此外，同时具有TERTpm和TP53m的患者表现出显著更高的肿瘤复发风险（P < 0.05）和更短的无进展生存期（P < 0.05）。总体而言，我们的结果表明，TERTpm和TP53m的同时存在可能作为HCC肿瘤复发的有力预测指标和预后不良的标志物。
