Background/Objectives: We evaluated the relationship between the neoangiogenic transcriptomic signature (nTS) and clinical symptoms, treatment outcomes, and survival in hepatocellular carcinoma (HCC) patients.Methods: This study prospectively followed 328 patients in the derivation and 256 in the validation cohort (with a median follow-up of 31 and 22 months, respectively). The nTS was associated with disease presentation, treatments administered, and overall survival rates. Additionally, this study investigated how multiple treatments influenced changes in nTS status and alterations in microRNA expression.Results: The nTS was identified in 27.4% of patients, linked to aggressive features like multifocality and elevated alpha-fetoprotein (AFP), a pattern consistent with that of the validation cohort. Most patients in both cohorts received treatment for HCC. nTS+ patients had limited access to, and benefited less from, liver transplantation or radiofrequency ablation (RFA) compared to nTS− patients. By the end, 78.9% had died, with nTS− patients showing better median survival and response to treatments than their nTS+ counterparts, who had lower survival across all treatment types. Among those who received transarterial chemoembolization (TACE), 31.2% (21/80 patients after the initial treatment and another four following a second TACE) transitioned from an nTS− to an nTS+ status. This shift was associated with lower survival and alterations in microRNA expressions related to oncogenic pathways.Conclusions: The nTS markedly influences treatment eligibility and survival in patients with HCC. Notably, the nTS can develop after repeated TACE procedures, significantly impacting patient survival and altering oncogenic microRNA expression patterns. These findings highlight the critical role of the nTS in guiding treatment decisions and prognostication in HCC management.
背景/目的:本研究旨在评估肝细胞癌(HCC)患者中新生血管生成转录组特征(nTS)与临床症状、治疗效果及生存期之间的关系。 方法:本研究前瞻性随访了328例推导队列患者和256例验证队列患者(中位随访时间分别为31个月和22个月)。分析nTS与疾病表现、治疗方案及总生存率之间的关联,并探讨多种治疗方式对nTS状态变化及微RNA表达改变的影响。 结果:27.4%的患者检测到nTS,该特征与多灶性、甲胎蛋白(AFP)升高等侵袭性表现相关,这一模式在验证队列中保持一致。两个队列中大多数患者接受了HCC治疗。与nTS阴性患者相比,nTS阳性患者接受肝移植或射频消融(RFA)治疗的机会更少、获益更低。随访结束时,78.9%的患者死亡,nTS阴性患者的中位生存期和治疗反应均优于nTS阳性患者,后者在所有治疗类型中均表现出更低的生存率。在接受经动脉化疗栓塞(TACE)治疗的患者中,31.2%(首次治疗后21/80例,二次TACE后另有4例)从nTS阴性转为nTS阳性状态,这种转变与生存率下降及致癌通路相关微RNA表达改变有关。 结论:nTS显著影响HCC患者的治疗选择与生存预后。值得注意的是,重复TACE治疗后可能出现nTS特征,该变化会显著降低患者生存率并改变致癌性微RNA表达模式。这些发现揭示了nTS在指导HCC治疗决策和预后评估中的关键作用。