Several lines of epidemiological and biochemical evidence support the association
of type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC). T2DM has been shown
to impinge on the transcriptome of colon tumor cells, promoting their proliferation
and invasion. In order to gain insight into diabetes-specific modulation of colon
cancer signaling, we analyzed gene expression patterns of more than five hundred genes
encoding signaling proteins on TaqMan OpenArray panels from colonoscopic colorectal
tumor samples of type 2 diabetic and non-diabetic patients. In total, 48 transcripts
were found to be differentially expressed in tumors of T2DM patients as compared to
healthy colon samples. Enrichment analysis with the g:GOSt (Gene Ontology Statistics)
functional profiling tool revealed that the underlying genes can be classified into
five signaling pathways (in decreasing order of significance: Wnt (wingless-type)/beta-catenin;
Hippo; TNF (tumor necrosis factor); PI3K/Akt (phosphoinositide-3 kinase/protein kinase
B), and platelet activation), implying that targeted downregulation of these signaling
cascades might help combat CRC in diabetic patients. Transcript levels of some of
the differentially expressed genes were also measured from surgically removed diabetic
and non-diabetic CRC specimens by individual qPCR (quantitative real-time PCR) assays
using the adjacent normal tissue mRNA levels as an internal control. The most significantly
altered genes in diabetic tumor samples were largely different from those in non-diabetic
ones, implying that T2DM profoundly alters the expression of signaling genes and presumably
the biological characteristics of CRC.
