Zhong Guangcai, Guo Chong, Shang Yangli, Cui Zelong, Zhou Minran, Sun Mingshan, Fu Yue, Zhang Lu, Feng Huimin, Chen Chunyan
Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
The Second Hospital of Shandong University, Jinan, China.
Front Genet. 2023 Jan 4;13:1029717. doi: 10.3389/fgene.2022.1029717. eCollection 2022.
Pyroptosis, a programmed cell death (PCD) with highly inflammatory form, has been recently found to be associated with the origin of hematopoietic malignancies. Long noncoding RNA (lncRNA) had emerged as an essential mediator to regulate gene expression and been involved in oncogenesis. However, the roles of pyroptosis-related lncRNA (PRlncRNA) in acute myeloid leukemia (AML) have not yet been completely clarified. We collected AML datasets from public databases to obtain PRlncRNA associated with survival and constructed a PRlncRNA signature using Lasso-Cox regression analysis. Subsequently, we employed RT-PCR to confirm its expression difference and internal training to further verify its reliability. Next, AML patients were classified into two subgroups by the median risk score. Finally, the differences between two groups in immune infiltration, enrichment analysis and drug sensitivity were further explored. A PRlncRNA signature and an effective nomogram combined with clinicopathological variables to predict the prognosis of AML were constructed. The internal validations showed that the PRlncRNA risk score model was an accurate and productive indicator to predict the outcome of AML. Furthermore, this study indicated that higher inflammatory cell and immunosuppressive cells, and less sensitive to conventional chemotherapy drugs were highlighted in the high-risk group. Through comprehensive analysis of PRlncRNA model, our study may offer a valuable basis for future researches in targeting pyroptosis and tumor microenvironment (TME) and provide new measures for prevention and treatment in AML.
细胞焦亡是一种具有高度炎症形式的程序性细胞死亡（PCD），最近被发现与造血系统恶性肿瘤的起源有关。长链非编码RNA（lncRNA）已成为调节基因表达的重要介质，并参与肿瘤发生。然而，细胞焦亡相关lncRNA（PRlncRNA）在急性髓系白血病（AML）中的作用尚未完全阐明。我们从公共数据库收集AML数据集以获得与生存相关的PRlncRNA，并使用套索-考克斯回归分析构建PRlncRNA特征。随后，我们采用逆转录-聚合酶链反应（RT-PCR）来确认其表达差异，并进行内部训练以进一步验证其可靠性。接下来，根据中位风险评分将AML患者分为两个亚组。最后，进一步探讨两组在免疫浸润、富集分析和药物敏感性方面的差异。构建了一个PRlncRNA特征和一个结合临床病理变量来预测AML预后的有效列线图。内部验证表明，PRlncRNA风险评分模型是预测AML预后的准确且有效的指标。此外，本研究表明，高危组中炎症细胞和免疫抑制细胞较高，且对传统化疗药物不太敏感。通过对PRlncRNA模型的综合分析，我们的研究可能为未来针对细胞焦亡和肿瘤微环境（TME）的研究提供有价值的基础，并为AML的预防和治疗提供新的措施。
