■新的证据已经证明,人类内源性逆转录病毒(HERV)在急性髓系白血病(AML)的发病机理中起着至关重要的作用。而影响AML患者预后的特定HERV尚未完全了解。
■在这项研究中,进行了系统的探索,以确定AML的潜在预后性HERV,来自TCGA和GTEx数据库。使用GO进行差异分析和功能富集研究,KEGG,GSEA,和GSVA。应用ESTIMATE算法探索AML中HERV的免疫浸润。使用ROC分析以预测的年度准确性评估预后风险评分模型。
■两种HERVSuppressyn和Syncytin-2被鉴定为有希望的预后生物标志物,基于ROC分析,AML与TCGA健康队列之间具有较高的辨别能力。与健康个体相比,他们在AML患者中的表达明显更高,但与白种人等亚组的良好临床结果相关。较低的白细胞计数,有利和中间风险,和NPM1或IDH1突变。Suppressyn和Syncytin-2参与免疫相关通路,并与多种免疫浸润细胞表现出相关性,比如T细胞,肥大细胞,和肿瘤相关的巨噬细胞。最后,我们建立了一个联合Suppressyn和Syncytin-2的预后风险评分模型,其中高风险评分与更好的预后相关.
■集体,我们的研究结果表明,Suppressyn和Syncytin-2可能是AML患者有价值的诊断和预后生物标志物,同时强调HERV激活之间的联系,免疫原性,和未来的治疗目标。
Emerging evidence has proven that human endogenous retroviruses (HERVs) play a critical role in the pathogenesis of Acute Myeloid Leukemia (AML), whereas the specific HERVs influencing the prognosis of AML patients have yet to be fully understood.
In this study, a systematic exploration was achieved to identify potential prognostic HERVs for AML, sourced from TCGA and GTEx database. Differential analysis and functional enrichment studies were conducted using GO, KEGG, GSEA, and GSVA. The ESTIMATE algorithm was applied to explore the immune infiltration of HERVs in AML. A prognostic risk-score model was evaluated with predicted yearly accuracy using ROC analysis.
Two HERVs Suppressyn and Syncytin-2, were identified as promising prognostic biomarkers, with high discrimination ability based on ROC analysis between AML and healthy cohorts from TCGA. Their expression was notably higher in AML patients compared to those in healthy individuals but correlates with favorable clinical outcomes in sub-groups such as white race, lower WBC counts, favorable and intermediate risks, and NPM1 or IDH1 mutation. Suppressyn and Syncytin-2 participated in immune-related pathways and exhibited correlations with multiple immune infiltration cells, such as T cells, mast cells, and tumor-associated macrophages. Finally, we developed a prognostic risk-scoring model combining Suppressyn and Syncytin-2, where a high risk-score is associated with better prognosis.
Collectively, our findings revealed that Suppressyn and Syncytin-2 may act as valuable diagnostic and prognostic biomarkers for individuals with AML, while highlighting links between HERV activation, immunogenicity, and future therapeutic targets.