鉴定与软组织肉瘤免疫微环境相关的预后 lncRNA。

Identification of Prognostic lncRNA Related to the Immune Microenvironment of Soft Tissue Sarcoma.

机构信息

Orthopaedic Institute, Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 708 Renmin Rd., Suzhou, Jiangsu 215007, China.

Department of Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

出版信息

Biomed Res Int. 2022 Feb 2;2022:9471558. doi: 10.1155/2022/9471558. eCollection 2022.

DOI:10.1155/2022/9471558

PMID:35155682

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8832153/

Abstract

BACKGROUND

Soft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long noncoding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They perform preprocessing, splicing, transport, degradation, and translation of mRNA to achieve posttranscriptional level regulation, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators.

OBJECTIVE

The objective of the present study was to identify immune microenvironment-related lncRNAs that can be used to predict soft tissue sarcomas.

METHODS

Clinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and coexpression analysis. The Cox regression model and Kaplan-Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. We constructed an mRNA-lncRNA network by Cytoscape software. Finally, qRT-PCR was used to verify the difference in the expression of the lncRNAs in normal cells and sarcoma cells.

RESULTS

Unsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan-Meier (K-M) survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established. qRT-PCR results showed that the expression of AC108134.3 and AL031717.1 was significantly different in normal and sarcoma cells.

CONCLUSION

In summary, the experimental results showed that lncrnA associated with immune microenvironment was related to tumor, which may provide a new idea for immunotherapy of STS.

摘要

背景

软组织肉瘤是一种恶性程度高、预后差的恶性肿瘤，起源于间叶组织。长链非编码 RNA（lncRNA）参与体内的各种生物和病理过程。它们通过预处理、剪接、运输、降解和 mRNA 的翻译来实现转录后水平的调节，从而导致肿瘤的发生、侵袭和转移。因此，它们与早期诊断和预后标志物高度相关。

目的

本研究旨在鉴定可用于预测软组织肉瘤的免疫微环境相关 lncRNA。

方法

从 cBioPortal 数据库获取临床数据和随访数据，从 The Cancer Genome Atlas（TCGA）数据库获取用于模型结构的 RNA 测序数据。通过差异表达分析和共表达分析筛选 lncRNA。使用 Cox 回归模型和 Kaplan-Meier 分析研究免疫微环境中 lncRNA 与软组织肉瘤预后的关系。然后进行无监督聚类分析以发现筛选 lncRNA 对疾病的影响。通过 Cytoscape 软件构建 mRNA-lncRNA 网络。最后，使用 qRT-PCR 验证正常细胞和肉瘤细胞中 lncRNA 的表达差异。

结果

未监督聚类分析显示，筛选出的 210 个 lncRNA 与肿瘤免疫微环境具有很强的相关性。构建了包含七个和五个与肿瘤微环境相关的 lncRNA 的两个特征，用于预测总生存期（OS）和无病生存期（DFS）。Kaplan-Meier（K-M）生存曲线显示，高风险和低风险组患者的预后差异有统计学意义，低风险组的预后明显好于高风险组。建立了两个具有预测能力的列线图。qRT-PCR 结果表明，AC108134.3 和 AL031717.1 在正常和肉瘤细胞中的表达差异显著。