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

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.