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.

Overview of Transcriptomic Research on Type 2 Diabetes: Challenges and Perspectives

“…For instance, the cancer signaling pathway was shown to be the most upregulated pathway in elderly individuals with T2D compared to older people without T2D. In addition, this study also confirmed immune inflammation in T2D, showing the upregulation of T-cell activation and migration and inflammation pathways [31]. These findings reaffirm existing evidence of an increased risk of cancer among T2D patients due to hyperinsulinemia, hyperglycemia, or chronic inflammation [78].…”

Polyunsaturated fatty acid intake and incidence of type 2 diabetes in adults: a dose response meta-analysis of cohort studies

“…Type 2 diabetes (T2D) accounts for 90–95% of all diabetes cases and is a complex metabolic disorder characterized by insufficient insulin secretion and hyperglycemia caused by insulin resistance (IR) [ 1 , 2 ]. It is estimated that the global prevalence of T2D will increase from 171 million people in 2000 to 366 million people in 2030 [ 3 ], which will have a devastating effect on overall health [ 4 ].…”