The construction and analysis of tumor-infiltrating immune cell and ceRNA networks in recurrent soft tissue sarcoma
The construction and analysis of tumor-infiltrating immune cell and ceRNA networks in recurrent soft tissue sarcoma
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复发性软组织肉瘤肿瘤浸润免疫细胞和ceRNA网络的构建和分析。
DOI：
10.18632/aging.102424
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发表时间：
2019-11-30
期刊：
影响因子：
5.2
通讯作者：
Huang, Zongqiang
中科院分区：
文献类型：
--
作者：
Huang, Runzhi;Meng, Tong;Huang, Zongqiang
软组织肉瘤（STS）是最具挑战性的肿瘤之一，医学肿瘤学家，具有较高的复发率初次切除后。本研究基于TCGA数据库中259例原发性肉瘤和3例局部复发样本的基因表达谱，建立了包括7个复发和总生存期（OS）相关基因（LPP-AS 2、MUC 1、GAB 2、hsa-let-7i-5 p、hsa-let-7 f-5 p、hsa-miR-101- 3 p和hsa-miR-1226- 3 p）的复发STS特异性竞争性内源性RNA（ceRNA）网络。应用CIBERSORT算法估计肉瘤中免疫细胞的比例。基于5种复发和OS相关免疫细胞（NK细胞活化、树突状细胞静息、肥大细胞静息、肥大细胞活化和巨噬细胞M1），我们构建了复发STS特异性免疫细胞网络。两个列线图均具有良好的可靠性（5年生存率的曲线下面积（AUC）分别为0.724和0.773）。然后进行共表达分析以鉴定复发性STS特异性免疫细胞和ceRNA之间的潜在调控网络。hsa-miR-1226- 3 p与MUC 1显著相关，树突状细胞静息与hsa-miR-1226- 3 p相关。此外，MUC 1和树突状细胞标志物CD 11 c的表达也通过免疫组织化学（IHC）测定和多维数据库进行了验证。结论：hsa-miR-1226- 3 p调控MUC 1的可能机制及树突状细胞的静息状态可能在STS复发中发挥重要作用。这些发现可能为复发性STS提供潜在的预后生物标志物和治疗靶点。
Soft tissue sarcoma (STS) is one of the most challenging tumors for medical oncologists, with a high rate of recurrence after initial resection. In this study, a recurrent STS-specific competitive endogenous RNA (ceRNA) network including seven recurrence and overall survival (OS)-associated genes (LPP-AS2, MUC1, GAB2, hsa-let-7i-5p, hsa-let-7f-5p, hsa-miR-101-3p and hsa-miR-1226-3p) was established based on the gene expression profiling of 259 primary sarcomas and 3 local recurrence samples from the TCGA database. The algorithm "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)" was applied to estimate the fraction of immune cells in sarcomas. Based on 5 recurrence and OS-associated immune cells (NK cells activated, dendritic cells resting, mast cells resting, mast cells activated and macrophages M1), we constructed a recurrent STS-specific immune cells network. Both nomograms were identified to have good reliabilities (Area Under Curve (AUC) of 5-year survival is 0.724 and 0.773, respectively). Then the co-expression analysis was performed to identify the potential regulation network among recurrent STS-specific immune cells and ceRNAs. Hsa-miR-1226-3p and MUC1 were significantly correlated and dendritic cells resting was related to hsa-miR-1226-3p. Additionally, the expression of MUC1 and dendritic cell marker CD11c were also verified by immunohistochemistry (IHC) assay and multidimensional databases. In conclusion, this study illustrated the potential mechanism of hsa-miR-1226-3p regulating MUC1 and dendritic cells resting might play an important role in STS recurrence. These findings might provide potential prognostic biomarkers and therapeutic targets for recurrent STS.