Abstract
The mammalian orosomucoid-like gene family (ORMDL), containing ORMDL1, ORMDL2, and ORMDL3, is the important regulator of sphingolipid metabolism, which is relevant to cell growth, proliferation, migration, and invasion. Since the role of ORMDL1 in cancers remained unclear, the main purpose of our study was to explore the expression patterns and prognostic values of ORMDL1 in different tumors, especially in cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B cell lymphoma (DLBCL), acute myeloid leukemia (LAML), and thymoma (THYM). Bioinformatics tools including GEPIA, CCLE, LinkedOmics, cBioPortal, and TIMER databases were used. As a result, the expression levels of ORMDL1 in tumor tissues and normal tissues varied in different cancers, especially significantly upregulated in CHOL, DLBCL, LAML, and THYM. Moreover, ORMDL1 mRNA was also highly expressed in cell lines of DLBCL and LAML. Further studies showed that ORMDL1 overexpression was associated with poor prognosis in DLBCL, but not significant in CHOL, LAML, and THYM. Consistently, there were genetic alterations of ORMDL1 in DLBCL, and patients with genetic alterations indicated worse survival. Coexpressed genes and related biological events with ORMDL1 in DLBCL were found via LinkedOmics, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between ORMDL1 and cancer immune cells was investigated, and ORMDL1 expression was positively correlated with infiltrating levels of B cells. In conclusion, ORMDL1 is suggested to be a tumorigenic factor and considered as the potential therapeutic target and prognostic biomarker in DLBCL.
Highlights
The mammalian orosomucoid-like gene family (ORMDL), including ORMDL1, ORMDL2, and ORMDL3, encodes transmembrane proteins localized to the endoplasmic reticulum [1,2,3,4,5]
The differential expression of ORMDL1 in tumor samples and normal samples from all The Cancer Genome Atlas (TCGA) cancer types is listed in Figures 1(a) and 1(b)
The results indicated that ORMDL1 expression levels were significantly upregulated in CHOL, diffuse large B cell lymphoma (DLBCL), LAML, and THYM compared to their corresponding normal tissues (Figures 1(c) and 1(d))
Summary
The mammalian orosomucoid-like gene family (ORMDL), including ORMDL1, ORMDL2, and ORMDL3, encodes transmembrane proteins localized to the endoplasmic reticulum [1,2,3,4,5]. ORMDLs are primarily involved in negative feedback regulation of sphingolipid metabolism, ceramide synthesis, and unfolded protein response [3,4,5,6,7,8,9,10]. Inhibition of ORMDL1 led to enhanced SPT activity and increased sphingolipid levels [6]. For ORMDL3, it was closely associated with asthma risk in childhood [11, 12] and participated in cellular stress response [13], lymphocyte activation [14], and eosinophil trafficking [15]
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