Background/Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with significant racial and ethnic disparities in incidence, tumor biology, and clinical outcomes. Hispanic/Latino (H/L) patients tend to be diagnosed at younger ages and more advanced stages than Non-Hispanic White (NHW) patients, yet the molecular mechanisms underlying these disparities remain poorly understood. Key oncogenic pathways, including RTK/RAS, TGF-beta, WNT, PI3K, and TP53, play pivotal roles in tumor progression, treatment resistance, and response to targeted therapies. However, ethnicity-specific alterations within these pathways remain largely unexplored. This study aims to compare pathway-specific mutations in HCC between H/L and NHW patients, assess tumor mutation burden, and identify ethnicity-associated oncogenic drivers using publicly available datasets. Findings from this analysis may inform precision medicine strategies for improving early detection and targeted therapies in underrepresented populations. Methods: We conducted a bioinformatic analysis using publicly available HCC datasets to assess mutation frequencies in RTK/RAS, TGF-beta, WNT, PI3K, and TP53 pathway genes. This study included 547 patients, consisting of 69 H/L patients and 478 NHW patients. Patients were stratified by ethnicity (H/L vs. NHW) to evaluate differences in mutation prevalence. Chi-squared tests were used to compare mutation frequencies, while Kaplan–Meier survival analysis assessed overall survival differences associated with pathway-specific alterations in both populations. Results: Significant differences were observed in the RTK/RAS pathway-related genes, particularly in FGFR4 mutations, which were more prevalent in H/L patients compared to NHW patients (4.3% vs. 0.6%,p= 0.02). Additionally, IGF1R mutations exhibited borderline significance (7.2% vs. 2.9%,p= 0.07). In the PI3K pathway, INPP4B alterations were more frequent in H/L patients than in NHW patients (4.3% vs. 1%,p= 0.06), while, in the TGF-beta pathway, TGFBR2 mutations were more common in H/L patients (2.9% vs. 0.4%,p= 0.07), suggesting potential ethnicity-specific variations. Survival analysis revealed no significant differences in overall survival between H/L and NHW patients, indicating that molecular alterations alone may not fully explain survival disparities and suggesting a role for additional factors such as immune response, environmental exposures, or access to targeted therapies. Conclusions: This study provides one of the first ethnicity-focused analyses of key oncogenic pathway alterations in HCC, revealing distinct molecular differences between H/L and NHW patients. The findings suggest that RTK/RAS (FGFR4, IGF1R), PI3K (INPP4B), and TGF-beta (TGFBR2) pathway alterations may play a distinct role in HCC among H/L patients, while their prognostic significance in NHW patients remains unclear. These insights emphasize the importance of incorporating ethnicity-specific molecular profiling into precision medicine approaches to improve early detection, targeted therapies, and clinical outcomes in HCC, particularly for underrepresented populations.
**背景/目的：** 肝细胞癌是癌症相关死亡的主要原因，其发病率、肿瘤生物学特征和临床结局存在显著的种族和民族差异。与非西班牙裔白人患者相比，西班牙裔/拉丁裔患者往往在更年轻、疾病分期更晚时被诊断，然而导致这些差异的分子机制尚不清楚。包括RTK/RAS、TGF-β、WNT、PI3K和TP53在内的关键致癌通路在肿瘤进展、治疗耐药性和对靶向治疗的反应中起着关键作用。然而，这些通路中与特定民族相关的基因改变在很大程度上仍未得到探索。本研究旨在利用公开数据集，比较西班牙裔/拉丁裔与非西班牙裔白人HCC患者之间通路特异性突变，评估肿瘤突变负荷，并识别与民族相关的致癌驱动因素。该分析结果可能为制定精准医疗策略提供信息，以改善代表性不足人群的早期检测和靶向治疗。 **方法：** 我们利用公开的HCC数据集进行了生物信息学分析，以评估RTK/RAS、TGF-β、WNT、PI3K和TP53通路相关基因的突变频率。本研究共纳入547例患者，包括69例西班牙裔/拉丁裔患者和478例非西班牙裔白人患者。按民族（西班牙裔/拉丁裔 vs. 非西班牙裔白人）对患者进行分层，以评估突变流行率的差异。使用卡方检验比较突变频率，同时采用Kaplan-Meier生存分析评估与两个人群中通路特异性改变相关的总生存期差异。 **结果：** 在RTK/RAS通路相关基因中观察到显著差异，特别是FGFR4突变，其在西班牙裔/拉丁裔患者中的发生率高于非西班牙裔白人患者（4.3% vs. 0.6%，p=0.02）。此外，IGF1R突变显示出临界显著性（7.2% vs. 2.9%，p=0.07）。在PI3K通路中，INPP4B改变在西班牙裔/拉丁裔患者中比在非西班牙裔白人患者中更常见（4.3% vs. 1%，p=0.06）；而在TGF-β通路中，TGFBR2突变在西班牙裔/拉丁裔患者中更常见（2.9% vs. 0.4%，p=0.07），提示存在潜在的民族特异性变异。生存分析显示，西班牙裔/拉丁裔与非西班牙裔白人患者之间的总生存期无显著差异，表明单独的分子改变可能无法完全解释生存差异，并提示其他因素（如免疫反应、环境暴露或获得靶向治疗的机会）可能发挥作用。 **结论：** 本研究首次提供了针对HCC关键致癌通路改变的、以民族为重点的分析之一，揭示了西班牙裔/拉丁裔与非西班牙裔白人患者之间不同的分子差异。研究结果表明，RTK/RAS（FGFR4、IGF1R）、PI3K（INPP4B）和TGF-β（TGFBR2）通路改变可能在西班牙裔/拉丁裔患者的HCC中发挥独特作用，而其对于非西班牙裔白人患者的预后意义尚不明确。这些发现强调了将民族特异性分子谱分析纳入精准医疗方法的重要性，以改善HCC的早期检测、靶向治疗和临床结局，特别是对于代表性不足的人群。
肿瘤(癌症)患者之家