Development of a Novel Immune Infiltration-Related ceRNA Network and Prognostic Model for Sarcoma

Deyao Shi,Jianxiang Liu,Zengwu Shao,Binlong Zhong,Shidai Mu,Zhicai Zhang,Feifei Pu,Tongchuan He,Binwu Hu

doi:10.3389/fcell.2021.652300

Abstract

Due to the rarity and heterogeneity, it is challenging to explore and develop new therapeutic targets for patients with sarcoma. Recently, immune cell infiltration in the tumor microenvironment (TME) was widely studied, which provided a novel potential approach for cancer treatment. The competing endogenous RNA (ceRNA) regulatory network has been reported as a critical molecular mechanism of tumor development. However, the role of the ceRNA regulatory network in the TME of sarcoma remains unclear. In this study, gene expression data and clinical information were obtained from The Cancer Genome Atlas (TCGA) sarcoma datasets, and an immune infiltration-related ceRNA network was constructed, which comprised 14 lncRNAs, 13 miRNAs, and 23 mRNAs. Afterward, we constructed an immune infiltration-related risk score model based on the expression of IRF1, MFNG, hsa-miR-940, and hsa-miR-378a-5p, presenting a promising performance in predicting the prognosis of patients with sarcoma.

Highlights

Sarcomas are heterogeneous malignancies of mesenchymal origin, accounting for 1% of adult cancers, which are classified into more than 175 distinct subtypes (Steele and Pillay, 2020)
RNA-seq data and matched clinical information of 259 sarcoma patients were obtained from the Weighted gene co-expression network analysis (WGCNA) and Identification of the Immune Infiltration-Related Gene Module
All lncRNAs and mRNAs with the top 50% variance among samples were included in WGCNA, with one sample detected as the outlier in the sample clustering procedure

Summary

Introduction

Sarcomas are heterogeneous malignancies of mesenchymal origin, accounting for 1% of adult cancers, which are classified into more than 175 distinct subtypes (Steele and Pillay, 2020). It is difficult to make impressive progression in new therapeutic approaches for patients with sarcoma because of the rarity and heterogeneity (Miwa et al, 2019; Gamboa et al, 2020; Grünewald et al, 2020). The tumor microenvironment (TME), comprising extracellular matrix (ECM) and cellular components, has been documented to be firmly associated with the initiation and progression of sarcoma (Heymann et al, 2019). Combined regimens based on immune checkpoint inhibitors (anti-PD1 or anti-CTLA4) and modified T-cell therapies are currently being tested in specific sarcoma subtypes with a significant clinical benefit for the patients (Pollack et al, 2018; Dyson et al, 2019; Heymann et al, 2020).

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