目的:本研究旨在探讨ADH4在肝细胞癌(HCC)中的表达,其预后影响,及其免疫相关性为肝癌的预后和治疗提供了新的见解。
方法:使用GEO数据库严格选择HCC预后标记基因,套索回归,GEPIA,Kaplan-Meier和pROC分析。感兴趣的标记(ADH4,DNASE1L3,RDH16,LCAT,通过免疫组织化学(IHC)评估HCC和邻近组织中的HGFAC)。我们观察到ADH4在肝癌组织中表现出低表达水平,在正常肝组织中表现出高表达水平。然而,其余4个基因在肝细胞癌(HCC)组织和邻近的非癌组织之间没有任何统计学差异.因此,ADH4成为我们研究的主要焦点。ADH4表达通过全癌症和HCC数据集的符号秩检验和非配对Wilcoxon秩和检验进行验证。使用Kaplan-Meier确定临床意义和与临床病理变量的关联,TCGA数据的逻辑回归和Cox分析。使用TIMER2数据通过Spearman相关性分析探索ADH4相关的免疫应答。通过IHC确认HCC和非癌组织中的CD68、CD4和CD19蛋白水平。
结果:ADH4在各种癌症中显示出显著的下调,特别是在HCC中。此外,ADH4低表达与临床病理变量相关,可作为HCC患者的独立预后指标.此外,ADH4影响多种生化功能,并可能影响癌症的发展,预后,通过结合免疫细胞进行治疗。此外,在免疫水平上,ADH4的低表达模式是TME特异性的,这表明ADH4有可能作为癌症免疫治疗的靶点。
结论:这项研究强调了诊断,ADH4在肝癌中的预后和免疫调节作用。ADH4可以作为肝癌诊断和预后的有价值的生物标志物,以及免疫治疗干预的潜在目标。
OBJECTIVE: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment.
METHODS: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues.
RESULTS: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy.
CONCLUSIONS: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.