Cancer Signaling Transcriptome Is Upregulated in Type 2 Diabetes Mellitus

Abstract

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini–Hochberg-adjusted p-value were >1.30 and their absolute z-scores were >2.0 (≥2.0 meant “upregulation” and ≤ −2.0 “downregulation”). Cancer signaling pathways were the most upregulated ones in T2D (z-score = 2.63, −log(p-value) = 32.3; 88.5% (n = 906) of the total differentially expressed genes located in these pathways). In particular, integrin (z-score = 2.52, −log(p-value) = 2.03) and paxillin (z-score = 2.33, −log(p-value) = 1.46) signaling pathways were predicted to be upregulated, whereas the Rho guanosine diphosphate (Rho-GDP) dissociation inhibitor signaling pathway was predicted to be downregulated in T2D individuals (z-score = −2.14, −log(p-value) = 2.41). Our results suggest that, at transcriptional expression level, elderly individuals with T2D present an increased activation of signaling pathways related to neoplastic processes, T-cell activation and migration, and inflammation.

Keywords

• transcriptome
• microarray
• signaling pathways
• cancer
• type 2 diabetes