Upregulation of ATIC in multiple myeloma tissues based on tissue microarray and gene microarrays

Abstract

Purpose Multiple myeloma (MM) is characterized by the malignant proliferation of plasma cells, which produce a monoclonal immunoglobulin protein. The role of 5‐aminoimidazole‐4‐carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) has not yet been well studied in the area of MM. Thus, in the current study, we sought to examine the expression levels, including mRNA and protein levels of ATIC in MM. Methods Multiple myeloma microarray and RNA‐seq data were screened from the SRA, GEO, ArrayExpress, and Oncomine databases. The mRNA level of ATIC was extracted from the high throughput data, and the prognostic value was studied. The protein level of ATIC was also detected by in‐house immunohistochemistry on a tissue microarray. Potential signaling pathways were enriched with ATIC‐related genes in MM. Results Both the mRNA and protein levels of ATIC were significantly upregulated in MM samples as compared to normal samples. Furthermore, the summarized Standardized Mean Difference was 1.66 with 674 cases of MM based on 10 independent studies including the in‐house tissue microarray. The overall hazard ratio of ATIC in MM was 1.7 with 1631 cases of MM based on five microarrays. In the KEGG pathway analysis, the ATIC‐related genes were mainly enriched in the pathway of complement and coagulation cascades. Conclusion We provided the first evidence supporting the upregulation of ATIC may play an essential part in the tumorigenesis and development of MM. The promoting cancer capacity may be related to the pathway of complement and coagulation cascades.

Circ-ATIC regulates esophageal squamous cell carcinoma growth and metastasis through miR-1294/PBX3 pathway

“…ATIC is a critical bifunctional enzyme that catalyzes the final 2 steps of the purine de novo biosynthetic pathway [ 22 ]. Higher ATIC is associated with the progression of several cancers, such as ATIC hepatocellular cancer [ 23 ], multiple myeloma tissues [ 24 ] and lung adenocarcinoma [ 25 ]. It is clarified that ATIC-mediated assembly of the multienzyme purinosome complex is driven by hypoxia via HIF-1 [ 26 ].…”

NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2 Genetic Variations are Associated with Ventricular Septal Defect in the Chinese Tibetan Population Through Whole-Exome Sequencing

“… 22 The abnormal expression of ATIC is closely related to the prognosis of hepatocellular carcinoma patients and can cause significant changes in the proliferation and migration of hepatocellular carcinoma cells. 23 Other studies have also shown that the abnormal expression of ATIC is closely related to the occurrence of various diseases, including multiple myeloma, 24 lung cancer, 25 lymphoma, 26 etc. We found that ATIC gene was associated with VSD in the Chinese Tibetan population, and it was associated with ASD, ventricular disease.…”

Impact of Variants in the ATIC and ARID5B Genes on Therapeutic Failure with Imatinib in Patients with Chronic Myeloid Leukemia

“…The authors found that ATIC activates mTOR-S6 kinase 1 signaling and consequently stimulates the proliferation and migration of oncotic cells [ 25 ]. Furthermore, the gene has been associated with autophagy and an increased risk of developing HCC [ 26 ], lung cancer [ 27 ], and multiple myeloma [ 28 ].…”