ABSTRACT
The coronavirus disease (COVID-19) pandemic caused by SARS-CoV-2 is ongoing. Individuals with sarcoidosis tend to develop severe COVID-19; however, the underlying pathological mechanisms remain elusive. To determine common transcriptional signatures and pathways between sarcoidosis and COVID-19, we investigated the whole-genome transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with COVID-19 and sarcoidosis and conducted bioinformatic analysis, including gene ontology and pathway enrichment, protein-protein interaction (PPI) network, and gene regulatory network (GRN) construction. We identified 33 abnormally expressed genes that were common between COVID-19 and sarcoidosis. Functional enrichment analysis showed that these differentially expressed genes were associated with cytokine production involved in the immune response and T cell cytokine production. We identified several hub genes from the PPI network encoded by the common genes. These hub genes have high diagnostic potential for COVID-19 and sarcoidosis and can be potential biomarkers. Moreover, GRN analysis identified important microRNAs and transcription factors that regulate the common genes. This study provides a novel characterization of the transcriptional signatures and biological processes commonly dysregulated in sarcoidosis and COVID-19 and identified several critical regulators and biomarkers. This study highlights a potential pathological association between COVID-19 and sarcoidosis, establishing a theoretical basis for future clinical trials.
ABSTRACT
Aberrant activation of calmodulin 1 (CALM1) has been reported in human cancers. However, comprehensive understanding of the role of CALM1 in most cancer types has remained unclear. We systematically analyzed the expression landscape, DNA methylation, gene alteration, immune infiltration, clinical relevance, and molecular pathway of CALM1 in multiple cancers using various online tools, including The Cancer Genome Atlas, cBioPortal and the Human Protein Atlas databases. Kaplan-Meier and receiver operating characteristic (ROC) curves were plotted to explore the prognostic and diagnostic potential of CALM1 expression. Multivariate analyses were used to evaluate whether the CALM1 expression could be an independent risk factor. A nomogram predicting the overall survival (OS) of patients was developed, evaluated, and compared with the traditional Tumor-Node-Metastasis (TNM) model using decision curve analysis. R language was employed as the main tool for analysis and visualization. Results revealed CALM1 to be highly expressed in most cancers, its expression being regulated by DNA methylation in multiple cancers. CALM1 had a low mutation frequency (within 3%) and was associated with immune infiltration. We observed a substantial positive correlation between CALM1 expression and macrophage and neutrophil infiltration levels in multiple cancers. Different mutational forms of CALM1 hampered immune cell infiltration. Additionally, CALM1 expression had high diagnostic and prognostic potential. Multivariate analyses revealed CALM1 expression to be an independent risk factor for OS. Therefore, our newly developed nomogram had a higher clinical value than the TNM model. The concordance index, calibration curve, and time-dependent ROC curves of the nomogram exhibited excellent performance in terms of predicting the survival rate of patients. Moreover, elevated CALM1 expression contributes to the activation of cancer-related pathways, such as the WNT and MAPK pathways. Overall, our findings improved our understanding of the function of CALM1 in human cancers.
