Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
Guangxi Medical University, Nanning, Guangxi, China.
J Cancer Res Clin Oncol. 2024 Apr 18;150(4):203. doi: 10.1007/s00432-024-05682-w.
Necroptosis-related long noncoding RNAs (lncRNAs) play crucial roles in cancer initiation and progression. Nevertheless, the role and mechanism of necroptosis-related lncRNAs in soft tissue sarcomas (STS) is so far unknown and needs to be explored further.
Clinical and genomic data were obtained from the UCSC Xena database. All STS patients' subclusters were performed by unsupervised consensus clustering method based on the prognosis-specific lncRNAs, and then assessed their survival advantage and immune infiltrates. In addition, we explored the pathways and biological processes in subclusters through gene set enrichment analysis. At last, we established the necroptosis-related lncRNA-based risk signature (NRLncSig) using the least absolute shrinkage and selection operator (LASSO) method, and explored the prediction performance and immune microenvironment of this signature in STS.
A total of 911 normal soft tissue samples and 259 STS patients were included in current study. 39 prognosis-specific necroptosis-related lncRNAs were selected. Cluster 2 had a worse survival than the cluster 1 and characterized by different immune landscape in STS. A worse outcome in the high-risk group was observed by survival analysis and indicated an immunosuppressive microenvironment. The ROC curve analyses illustrated that the NRLncSig performing competitively in prediction of prognosis for STS patients. In addition, the nomogram presents excellent performance in predicting prognosis, which may be more beneficial towards STS patients' treatment.
Our result indicated that the NRLncSig could be a good independent predictor of prognosis, and significantly connected with immune microenvironment, thereby providing new insights into the roles of necroptosis-related lncRNAs in STS.
坏死性凋亡相关长链非编码 RNA（lncRNA）在癌症的发生和发展中起着至关重要的作用。然而，坏死性凋亡相关 lncRNA 在软组织肉瘤（STS）中的作用和机制尚不清楚，需要进一步研究。
从 UCSC Xena 数据库中获取临床和基因组数据。基于预后特异性 lncRNA，采用无监督共识聚类方法对所有 STS 患者的亚群进行聚类，然后评估其生存优势和免疫浸润情况。此外，我们通过基因集富集分析探讨了亚群中的途径和生物学过程。最后，我们使用最小绝对收缩和选择算子（LASSO）方法建立了基于坏死性凋亡相关 lncRNA 的风险特征（NRLncSig），并探讨了该特征在 STS 中的预测性能和免疫微环境。
本研究共纳入 911 例正常软组织样本和 259 例 STS 患者。筛选出 39 个与坏死性凋亡相关的预后特异性 lncRNA。与簇 1 相比，簇 2 的生存情况更差，并且在 STS 中具有不同的免疫景观。生存分析显示高危组的预后较差，并表明存在免疫抑制微环境。ROC 曲线分析表明，NRLncSig 在预测 STS 患者预后方面具有竞争力。此外，列线图在预测预后方面表现出优异的性能，这可能对 STS 患者的治疗更有利。
我们的研究结果表明，NRLncSig 可以作为预后的独立预测因子，与免疫微环境密切相关，从而为坏死性凋亡相关 lncRNA 在 STS 中的作用提供了新的见解。
