The Construction and Comprehensive Analysis of ceRNA Networks and Tumor-Infiltrating Immune Cells in Bone Metastatic Melanoma
FRONTIERS IN GENETICS
Authors: Huang, Runzhi; Zeng, Zhiwei; Li, Guangyu; Song, Dianwen; Yan, Penghui; Yin, Huabin; Hu, Peng; Zhu, Xiaolong; Chang, Ruizhi; Zhang, Xu; Zhang, Jie; Meng, Tong; Huang, Zongqiang
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 Cancer Genome Atlas database, was 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 long noncoding RNA-microRNA and 15 pairs of microRNA-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 (area under curve of 3-year survival: 0.899; 5-year survival: 0.885; and concordance index: 0.780) with significant ceRNAs or immune cells, to predict the prognosis of patients. Conclusions: In this study, we suggest that bone metastasis in melanoma might be related to AL118506.1 and its role in regulating thrombospondin 2 and T follicular helper cells. Two nomograms were constructed to predict the prognosis of patients with melanoma and demonstrated their value in improving the personalized management.
Identification of Microenvironment-Related Prognostic Genes in Bladder Cancer Based on Gene Expression Profile
FRONTIERS IN GENETICS
Authors: Luo, Yongxiang; Zeng, Guohua; Wu, Song
Abstract
Background and Objective: Bladder cancer is the most common tumor in the urinary system, with a higher incidence in men than in women and a high recurrence rate. However, the mechanism of recurrence is still unclear, and it is urgent to clarify the pathophysiological mechanism of bladder cancer. To provide theoretical basis for the development of new therapies, investigating the effect of tumor microenvironment on the prognosis of bladder cancer is necessary. Methods: We applied the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm to the downloaded TCGA (The Cancer Genome Atlas) transcriptome data to obtain the immune scores and stromal scores of each sample, and then divided the samples into two groups: high and low immune scores (or high and low stromal scores), and found that some differential genes were associated with poor prognosis of patients. We then performed protein-protein interaction (PPI) network analysis to explore the relationship between these differentially expressed genes. Moreover, we also performed (Gene Ontology) GO and (Kyoto Encyclopedia of Genes and Genomes) KEGG analyses to explore the potential functions of differentially expressed genes. Finally, our results were validated in an independent dataset. Results: We identified 136 tumor microenvironment-related genes associated with poor prognosis of bladder cancer. GO annotation and KEGG pathway enrichment analysis found that these genes are mainly involved in extracellular matrix, Focal adhesion and phosphatidylinositol 3 kinase-protein kinaseB (PI3k-Akt) signaling pathway. Next, PPI network analysis revealed some hub genes including Versican (VCAN), Thrombospondin 1 (THBS1) and Thrombospondin 1 (THBS2). Finally, 27 genes were further verified in the independent data set. Conclusions: We found 27 tumor microenvironment-related genes of bladder cancer, which are associated with poor prognosis of bladder cancer. These genes may inspire researchers to develop new treatments for bladder cancer.