The Construction and Analysis of ceRNA Network and Immune Infiltration in Kidney Renal Clear Cell Carcinoma

Abstract

Background: Kidney renal clear cell carcinoma (KIRC) has the highest invasion, mortality and metastasis of the renal cell carcinomas and seriously affects patient’s quality of life. However, the composition of the immune microenvironment and regulatory mechanisms at transcriptomic level such as ceRNA of KIRC are still unclear.Methods: We constructed a ceRNA network associated with KIRC by analyzing the long non-coding RNA (lncRNA), miRNA and mRNA expression data of 506 tumor tissue samples and 71 normal adjacent tissue samples downloaded from The Cancer Genome Atlas (TCGA) database. In addition, we estimated the proportion of 22 immune cell types in these samples through “The Cell Type Identification by Estimating Relative Subsets of RNA Transcripts.” Based on the ceRNA network and immune cells screened by univariate Cox analysis and Lasso regression, two nomograms were constructed to predict the prognosis of patients with KIRC. Receiver operating characteristic curves (ROC) and calibration curves were employed to assess the discrimination and accuracy of the nomograms. Consequently, co-expression analysis was carried out to explore the relationship between each prognostic gene in a Cox proportional hazards regression model of ceRNA and each survival-related immune cell in a Cox proportional hazards regression model of immune cell types to reveal the potential regulatory mechanism.Results: We established a ceRNA network consisting of 12 lncRNAs, 25 miRNAs and 136 mRNAs. Two nomograms containing seven prognostic genes and two immune cells, respectively, were successfully constructed. Both ROC [area under curves (AUCs) of 1, 3, and 5-year survival in the nomogram based on ceRNA network: 0.779, 0.747, and 0.772; AUCs of 1, 3, and 5-year survivals in nomogram based on immune cells: 0.603, 0.642, and 0.607] and calibration curves indicated good accuracy and clinical application value of both models. Through co-correlation analysis between ceRNA and immune cells, we found both LINC00894 and KIAA1324 were positively correlated with follicular helper T (Tfh) cells and negatively correlated with resting mast cells.Conclusion: Based on the ceRNA network and tumor-infiltrating immune cells, we constructed two nomograms to predict the survival of KIRC patients and demonstrated their value in improving the personalized management of KIRC.

Comprehensive analysis of PTEN‐related ceRNA network revealing the key pathways WDFY3‐AS2 ‐ miR‐21‐5p/miR‐221‐3p/miR‐222‐3p ‐ TIMP3 as potential biomarker in tumorigenesis and prognosis of kidney renal clear cell carcinoma

“…miRNA plays an important role in tumor diagnosis, prognosis, and treatment. 41,42 In our study, miR-21-5p, miR-221-3p, and miR-222-3p…”

Multiomics Immune-Related lncRNA Analysis of Oral Squamous Cell Carcinoma and Its Correlation with Prognosis

“…In recent years, with the rise of gene expression profiling chips, strengthening the core method for analyzing the tumor gene structure of OSCC patients is essential for guiding clinical treatment [ 17 ]. Other scholars have found [ 18 , 19 ] that the lncRNA-mediated complex network can regulate a large number of coding genes. At present, lncRNA and its target genes have become a hot topic in oncology research, and more and more studies have confirmed that differentially expressed lncRNA can be involved in the development and progression of OSCC [ 20 ].…”

Long Noncoding RNAs as Orchestrators of CD4+ T-Cell Fate

“…One study demonstrated that the lncRNA MALAT1 is overexpressed in T cell subsets but is not a critical regulator of T cells; furthermore, MALAT1 has been shown to be nonessential for Tfh-cell differentiation ( Yao et al, 2018 ). Although lncRNAs have not yet been shown to regulate Tfh-cell differentiation, relevant sequencing studies have indicated that many lncRNAs are relevant to Tfh pedigree transcription factors and cytokines ( Deng et al, 2021 ; Zhang et al, 2021 ). Therefore, the roles and specific mechanisms of lncRNAs in Tfh-cell differentiation are waiting for further study.…”