ABSTRACT
Objective: Interferon-γ (IFN-γ) encoded by IFNG gene is a pleiotropic molecule linked with inflammatory cell death mechanisms. This work aimed to determine and characterize IFNG and co-expressed genes, and to define their implications in breast carcinoma (BRCA). Methods: Transcriptome profiles of BRCA were retrospectively acquired from public datasets. Combination of differential expression analysis with WGCNA was conducted for selecting IFNG-co-expressed genes. A prognostic signature was generated through Cox regression approaches. The tumor microenvironment populations were inferred utilizing CIBERSORT. Epigenetic and epitranscriptomic mechanisms were also probed. Results: IFNG was overexpressed in BRCA, and connected with prolonged overall survival and recurrence-free survival. Two IFNG-co-expressed RNAs (AC006369.1, and CCR7) constituted a prognostic model that acted as an independent risk factor. The nomogram composed of the model, TNM, stage, and new event owned the satisfying efficacy in BRCA prognostication. IFNG, AC006369.1, and CCR7 were closely linked with the tumor microenvironment components (e.g., macrophages, CD4/CD8 T cells, NK cells), and immune checkpoints (notably PD1/PD-L1). Somatic mutation frequencies were 6%, and 3% for CCR7, and IFNG, and high amplification potentially resulted in their overexpression in BRCA. Hypomethylated cg05224770 and cg07388018 were connected with IFNG and CCR7 upregulation, respectively. Additionally, transcription factors, RNA-binding proteins, and non-coding RNAs possibly regulated IFNG and co-expressed genes at the transcriptional and post-transcriptional levels. Conclusion: Collectively, our work identifies IFNG and co-expressed genes as prognostic markers for BRCA, and as possible therapeutic targets for improving the efficacy of immunotherapy.
ABSTRACT
Purpose: This study was aimed at identifying hub genes and ceRNA regulatory networks linked to prognosis in hepatocellular carcinoma (HCC) and to identify possible therapeutic targets. Methods: Differential expression analyses were performed to detect the differentially expressed genes (DEGs) in the four datasets (GSE76427, GSE6764, GSE62232, and TCGA). The intersected DEmRNAs were identified to explore biological significance by enrichment analysis. We built a competitive endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA. The mRNAs of the ceRNA network were used to perform Cox and Kaplan-Meier analyses to obtain prognosis-related genes, followed by the selection of genes with an area under the curve >0.8 to generate the random survival forest model and obtain feature genes. Furthermore, the feature genes were subjected to least absolute shrinkage and selection operator (LASSO) and univariate Cox analyses were used to identify the hub genes. Finally, the infiltration status of immune cells in the HCC samples was determined. Results: A total of 1923 intersected DEmRNAs were identified in four datasets and involved in cell cycle and carbon metabolism. ceRNA network was created using 10 lncRNAs, 67 miRNAs, and 1,923 mRNAs. LASSO regression model was performed to identify seven hub genes, SOCS2, MYOM2, FTCD, ADAMTSL2, TMEM106C, LARS, and KPNA2. Among them, TMEM106C, LARS, and KPNA2 had a poor prognosis. KPNA2 was considered a key gene base on LASSO and Cox analyses and involved in the ceRNA network. T helper 2 cells and T helper cells showed a higher degree of infiltration in HCC. Conclusion: The findings revealed seven hub genes implicated in HCC prognosis and immune infiltration. A corresponding ceRNA network may help reveal their potential regulatory mechanism.
