Comprehensive analysis of tumor microenvironment reveals prognostic ceRNA network related to immune infiltration in sarcoma.

Sarcoma (SARC) is the second most common solid tumor type in children and adolescents. The high level of tumor heterogeneity as well as aggressive behavior of SARCs bring serious difficulties to developing effective therapeutic strategies for clinical application. Therefore, it's of great importance to identify accurate biomarkers for early detection and prognostic prediction of SARCs. In this study, we characterized three subtypes of SARCs based on tumor immune infiltration levels (TIILs), and constructed a prognosis-related competing endogenous RNA (ceRNA) network to investigate molecular regulations in the sarcoma tumor microenvironment (TME). We further built a subnetwork consisting of mRNAs and lncRNAs which are targets of key miRNAs and strongly correlated with each other in the ceRNA network. After validation using public data and experiments in vivo and in vitro, we deeply dug the biological role of the miRNAs and lncRNAs in a subnetwork and their impact on TME. Altogether, 5 miRNAs (hsa-mir-125b-2, hsa-mir-135a-1, hsa-mir92a-2, hsa-mir-181a-2, and hsa-mir-214), 3 lncRNAs (LINC00641, LINC01146, and LINC00892), and 10 mRNAs (AGO2, CXCL10, CD86, CASP1, IKZF1, CD27, CD247, CD69, CCR2, and CSF2RB) in the subnetwork were identified as vital regulators to shape the TME. Based on the systematic network, we identified that Trichostatin A, a pan-HDAC inhibitor, could potentially regulate the TME of sarcoma thereby inhibiting the tumor growth. Our study identifies a ceRNA network as promising biomarker for SARC. This system provides a more comprehensive understanding and a novel perspective of how ceRNAs are involving in shaping sarcoma TME.

Citation

Dongliang Leng, Ziyi Yang, Heng Sun, Chengcheng Song, Chen Huang, Ka U Ip, Guokai Chen, Chu-Xia Deng, Xiaohua Douglas Zhang, Qi Zhao. Comprehensive analysis of tumor microenvironment reveals prognostic ceRNA network related to immune infiltration in sarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2023 Aug 01

PMID: 37527025

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