Abstract

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.

Highlights

  • Soft tissue sarcoma (STS) is a group of rare tumors including more than 50 different histological subtypes [1]

  • We identified the differential expressed Competing endogenous RNAs (ceRNAs) involved in recurrent STSs based on their gene expression profiling available from the TCGA (The Cancer Genome Atlas) database and used the algorithm “CIBERSORT” to quantify the proportions of immune cells

  • We inferred that the mechanism of hsamiR-1226-3p regulating Mucin 1 (MUC1) and dendritic cells resting might play an important role in STS recurrence

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Summary

Introduction

Soft tissue sarcoma (STS) is a group of rare tumors including more than 50 different histological subtypes [1]. It accounts for approximately 1% of adult malignancies and 15 % of pediatric malignancies [2, 3]. STS is derived from mesenchymal cell and usually divided into two broad categories: sarcomas of the soft www.aging-us.com tissues and sarcomas of the bone [2]. A complete resection is recommended for STS, but anatomic constraints hinder such efforts and local recurrence rate is high [5, 6]. There is a pressing need to explore the underlying mechanism of STS recurrence, which may provide potential prognostic factors and therapeutic targets for its treatment in the clinic

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