Impact Factor 3.517 | CiteScore 3.60
More on impact ›

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00828

The construction and comprehensive analysis of ceRNA networks and tumor-infiltrating immune cells in bone metastatic melanoma

 Runzhi Huang1, 2, Zhiwei Zeng1,  Guangyu Li1,  Dianwen Song3, Penghui Yan1,  Huabin Yin3, Peng Hu1, Xiaolong Zhu1, Ruizhi Chang1, Xu Zhang1,  Jie Zhang4*,  Tong Meng2* and  Zongqiang Huang1, 5*
  • 1Department of Orthopaedics, First Affiliated Hospital of Zhengzhou University, China
  • 2Spine Surgery Division, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University School of Medicine, China
  • 3Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China
  • 4Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, China
  • 5First Affiliated Hospital of Zhengzhou University, China

Abstract
Background/Aims: As a malignant and melanocytic tumor, cutaneous melanoma is the devastating skin tumor with high rates of recurrence and metastasis. Bone is the common metastatic location and bone metastasis may result in pathologic fracture, neurologic damage and severe bone pain. Although metastatic melanoma was reported to get benefits from immunotherapy, molecular mechanisms and immune microenviroment underlying the melanoma bone metastasis and prognostic factors are still unknown.
Methods: Gene expression profiling of 112 samples including 104 primary melanomas and 8 bone metastatic melanomas from the TCGA database, were assayed to construct a ceRNA network associated with bone metastases. Besides, we detected the fraction of 22 immune cell types in melanoma via the algorithm of “cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)”. Based on the significant ceRNAs or immune cells, we constructed nomograms to predict the prognosis of patients with melanoma. Ultimately, correlation analysis was implemented to discover the relationship between the significant ceRNA and immune cells to reveal the potential signaling pathways.
Results: We constructed a ceRNA network based on the interaction among 8 pairs of lncRNA-miRNA and 15 pairs of miRNA-mRNA. CIBERSORT and ceRNA integration analysis discovered that AL118506.1 has both significant prognostic value (P = 0.002) and high correlation with T follicular helper cells (P = 0.033). Meanwhile, T cells CD8 and Macrophages M2 were negatively correlated (P < 0.001). Moreover, we constructed two satisfactory nomograms (The Area Under Curve (AUC) of 3-year survival: 0.899; 5-year: 0.885 and Concordance Index: 0.780, respectively) with significant ceRNAs or immune cells, to predict the prognosis of patients.
Conclusions: In this study, we suggested that bone metastasis in melanoma might be related to AL118506.1 and its role in regulating Thrombospondin 2 (THBS2) and T follicular helper cells (Tfh cells). Two nomograms were constructed to predict the prognosis of patients with melanoma and demonstrated their value in improving the personalized management.

Keywords: Melanoma, bone metastasis, competing endogenous RNA network, immune cell, nomogram

Received: 26 Jun 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Huang, Zeng, Li, Song, Yan, Yin, Hu, Zhu, Chang, Zhang, Zhang, Meng and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Jie Zhang, Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China, jiezhang@tongji.edu.cn
MD. Tong Meng, Spine Surgery Division, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China, mengtong@medmail.com.cn
Prof. Zongqiang Huang, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, gzhuangzq@163.com