Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine

Abstract

Background Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. Methods Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin's concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. Results Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = − 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. Conclusions Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin's secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development.

Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents

“…Resistin was reportedly increased in subjects with rectal cancer and in correlation with insulin levels in CRC patients [76]. Similarly, our study demonstrated increased levels of resistin and its receptor adenylate cyclase-associated protein 1 in CRC [77]. Also, a meta-analysis pointed towards elevated resistin levels in CRC patients [78].…”

“…Therefore, the predominance of small, dense LDL represents a critical factor for the development and progression of atherosclerosis [182] and endothelial dysfunction, which both amplify the risk of cardiovascular events [181]. Some inflammatory cytokines, such as resistin, are closely associated with these LDL subspecies and seem to play a role in both diabetes and colon cancer development [77,183].…”

CAPt’n of Actin Dynamics: Recent Advances in the Molecular, Developmental and Physiological Functions of Cyclase-Associated Protein (CAP)

“…An increase in Resistin plasma levels and CAP1 expression in peripheral blood mononuclear cells has been reported in colorectal cancer patients (Mihajlovic et al, 2019). Resistin can also contribute to pancreatic cancer pathogenesis, since its levels are increased in pancreatic cancer patients and correlate positively with tumor grades.…”

The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis

“…Further, its higher expression is found associated with poor prognosis, nodal metastasis, and advanced cancer stage in colorectal cancer patients [ 126 ]. It is important to state that its expression was negatively associated with high density lipoprotein cholesterol (HDL-C) in colorectal cancer patients because of a possible interaction of its release with HDL-C [ 127 ].…”