HCC remains a lethal cancer type, with early detection being critical for improved patient outcomes. This study introduces a comprehensive methodological approach to identify the ITGA6 gene as a potential blood marker for early HCC (eHCC) detection. We initially analyzed the GSE114564 dataset encompassing various stages of liver disease, identifying 972 differentially expressed genes in HCC. A refined analysis yielded 59 genes specifically differentially expressed in early HCC, including ITGA6. Subsequent validation in multiple datasets confirmed the consistent upregulation of ITGA6 in HCC. In addition, when analyzing progression-free survival (PFS) within the entire patient cohort and overall survival (OS) specifically among patients classified as tumor grade G1, the group of patients characterized by high expression levels of ITGA6 displayed an elevated risk ratio in relation to prognosis. Further analyses demonstrated the predominant expression of ITGA6 in TECs and its enrichment in angiogenesis-related pathways. Additionally, positive correlations were found between ITGA6 expression and pro-tumorigenic immune cells, but not with anti-tumorigenic immune cells. Our study elucidates the potential of ITGA6 as a blood-based marker for HCC early detection and diagnosis and its complex interplay with the tumor microenvironment. Further research may lead to novel strategies for HCC management and patient care.
肝细胞癌(HCC)仍是一种致死率较高的癌症类型,早期检测对于改善患者预后至关重要。本研究提出了一种综合方法学策略,旨在鉴定ITGA6基因作为早期HCC(eHCC)检测的潜在血液标志物。我们首先分析了涵盖肝脏疾病不同阶段的GSE114564数据集,从中识别出972个在HCC中差异表达的基因。通过进一步筛选,确定了59个在早期HCC中特异性差异表达的基因,其中包括ITGA6。随后在多个数据集中的验证证实了ITGA6在HCC中持续上调的表达模式。此外,在对全体患者队列的无进展生存期(PFS)以及肿瘤分级为G1级患者的总生存期(OS)进行分析时发现,ITGA6高表达患者组的预后风险比显著升高。进一步分析显示,ITGA6主要在肿瘤内皮细胞中表达,并富集于血管生成相关通路。同时,ITGA6表达与促肿瘤免疫细胞呈正相关,而与抗肿瘤免疫细胞无显著关联。本研究阐明了ITGA6作为HCC早期检测和诊断的血液标志物的潜力,及其与肿瘤微环境的复杂相互作用。后续研究可能为HCC的治疗管理和患者护理提供新策略。