Lin Zhengjun, Pang Ke, Li Hongli, Zhang Xianghong, Wan Jia, Zheng Tao, Liu Tang, Peng Weijun
Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.
Xiangya School of Medicine, Central South University, Changsha, China.
Front Cell Dev Biol. 2021 Sep 24;9:709241. doi: 10.3389/fcell.2021.709241. eCollection 2021.
Increasing evidence has demonstrated that immune-related long non-coding RNAs (irlncRNAs) are critically involved in tumor initiation and progression and associated with the prognosis of various cancers. However, their role in soft tissue sarcoma (STS) remains significantly uninvestigated. Gene expression profiles were extracted from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) for the identification of irlncRNAs. Univariate analysis and modified least absolute shrinkage and selection operator (LASSO) penalized regression analysis were employed to determine differently expressed irlncRNA (DEirlncRNA) pairs of prognostic value, and subsequently, a risk signature based on DEirlncRNA pairs was established. Furthermore, Kaplan-Meier analysis and the area under the receiver operating characteristic curve (AUC) were used to assess survival differences and the predictive accuracy of the risk signature, respectively. Lastly, the correlation of irlncRNAs with immune characteristics and chemosensitivity in patients with STS were further investigated. A total of 1088 irlncRNAs were identified, and 311 irlncRNAs were distinguished as DEirlncRNAs. A total of 130 DEirlncRNA pairs were further identified as prognostic markers, and 14 pairs were selected for establishing a risk signature. The irlncRNA-based risk signature functioned as an independent prognostic marker for STS. Compared with the patients in the high-risk group, those in the low-risk group exhibited a better prognosis and were more sensitive to several chemotherapeutic agents. In addition, the irlncRNA-based risk signature was significantly associated with immune scores, infiltrating immune cells, and the expression of several immune checkpoints. In conclusion, our data revealed that the irlncRNA-based risk signature resulted in reliable prognosis, effectively predicted the immune landscape of patients with STS and was significantly correlated with chemosensitivity, thus providing insights into the potential role of irlncRNAs as prognostic biomarkers and novel therapeutic targets for STS.
越来越多的证据表明，免疫相关长链非编码RNA（irlncRNAs）在肿瘤的发生和发展中起关键作用，并与多种癌症的预后相关。然而，它们在软组织肉瘤（STS）中的作用仍未得到充分研究。从癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）中提取基因表达谱，以鉴定irlncRNAs。采用单因素分析和改进的最小绝对收缩和选择算子（LASSO）惩罚回归分析来确定具有预后价值的差异表达irlncRNA（DEirlncRNA）对，随后，基于DEirlncRNA对建立风险特征。此外，分别采用Kaplan-Meier分析和受试者工作特征曲线下面积（AUC）评估生存差异和风险特征的预测准确性。最后，进一步研究irlncRNAs与STS患者免疫特征和化疗敏感性的相关性。共鉴定出1088个irlncRNAs，其中311个irlncRNAs被鉴定为DEirlncRNAs。共进一步鉴定出130对DEirlncRNA对作为预后标志物，并选择14对建立风险特征。基于irlncRNA的风险特征可作为STS的独立预后标志物。与高危组患者相比，低危组患者预后更好，对几种化疗药物更敏感。此外，基于irlncRNA的风险特征与免疫评分、浸润免疫细胞和几种免疫检查点的表达显著相关。总之，我们的数据表明，基于irlncRNA的风险特征可得出可靠的预后，有效预测STS患者的免疫格局，并与化疗敏感性显著相关，从而为irlncRNAs作为STS预后生物标志物和新型治疗靶点的潜在作用提供了见解。
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