Title:ERH Impacts Patient Prognosis and Tumor Immune Microenvironment: A Pan-Cancer Analysis
Volume: 28
Issue: 5
Author(s): Qianhui Gong, Qiong Li, Zhichao Xu and Xiaobing Shen*
Affiliation:
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast
University, Nanjing, China
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast
University, Nanjing, China
Keywords:
ERH, pan-cancer analysis, tumor, immune infiltration, prognosis.
Abstract:
Background: The enhancer of rudimentary homolog (ERH) has been shown to play
significant roles in tumorigenesis and progression. However, few systematic pan-cancer analyses
about ERH have been described.
Methods: From the tumor immune estimation resource web server2.0 (TIMER2.0), the Genotype-
Tissue Expression database (GTEx) and the Gene Expression Profile Interactive Analysis
version 2 (GEPIA2) databases, we explored the expression profiles and prognostic significance
of ERH in 33 cancers. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the
Human Protein Atlas (HPA) databases were further used to examine the differential expression
of ERH at the protein level. The genetic alteration profile was obtained from the cBioPortal. The
correlation between ERH expression and the quantities of immune infiltrating cells was examined
by the TIMER tool. Spearman's correlation test was conducted to analyze the association
between ERH expression status and a number of prognostic indicators, including immune checkpoints,
TMB, MSI, immune neoantigen, MMR genes, and DNA methyltransferases. Protein-
Protein Interaction analyses were performed in the String and GeneMANIA databases, and enrichment
analysis and predicted signaling pathways were identified through GO and KEGG. To
make our results convincing, we validated them in six datasets in the Gene Expression Omnibus
(GEO) database. In addition, we verified the expression of ERH between gastric cancer tissues
and adjacent normal tissues by RT-qPCR.
Results: ERH expression was elevated in numerous tumors, and it was associated with the patient's
prognosis. Furthermore, the quantities of immune infiltrating cells and immune checkpoint
genes were remarkably associated with ERH. TMB and MSI were related to ERH expression in
14 and 15 cancer types, respectively. Moreover, the expression of ERH was strongly associated
with MMR defects in multiple cancer types, and almost all tumors showed co-expression of ERH
and four DNA methyltransferases. The results of GO and KEGG analysis confirmed that ERH
potentially impacts several important signaling pathways. Both the GEO datasets and the RTqPCR
experiment validated our previous analysis.
Conclusion: Our pan-cancer analysis demonstrated the characterization of ERH in multiple tumors.
ERH may be a valuable novel biological indicator for assessing immunotherapy efficacy
and prognosis in various malignancies.
