Hsa_circ_0054633 RNA a potential diagnostic biomarker for prediabetes, T2DM
The circular RNA (circRNA) hsa_circ_0054633 may be useful in the diagnosis of prediabetes and type 2 diabetes mellitus (T2DM), according to a single-centre study from China.
Peripheral blood samples from six healthy individuals and six T2DM patients were used to extract circRNAs for microarray analysis. Among the 489 circRNAs differentially expressed in the T2DM group (upregulated, 78; downregulated, 411), five candidate biomarkers (fold change >2.4; p<0.01) were identified: hsa_circ_0068087, hsa_circ_0054633, hsa_circ_0124636, hsa_circ_0139110 and hsa_circ_0018508.
The screened circRNAs were then validated in a second cohort consisting of 20 healthy controls, 20 individuals with prediabetes and 20 T2DM patients. There were no significant differences observed in the expression of hsa_circ_0124636 and hsa_circ_0139110 among the three groups, whereas that of hsa_circ_0018508 was similar between the prediabetes and T2DM groups but higher than in the control group. Only hsa_circ_0054633 and hsa_circ_0068087 differed significantly among the three groups, with the expression levels increasing gradually from the prediabetes group to the T2DM group to the control group. [Acta Diabetol 2017;54:23]
On receiver operating characteristic curve analysis, hsa_circ_0054633 achieved a higher accuracy for diagnosing prediabetes and T2DM compared with hsa_circ_0068087. The respective area under the curves (AUCs) were 0.747 (95 percent CI, 0.589 to 0.906; p=0.007) and 0.72 (0.562 to 0.878; p=0.017) with hsa_circ_0054633, and 0.692 (0.529 to 0.856; p=0.037) and 0.717 (0.557 to 0.878; p=0.019) with hsa_circ_0068087.
In a third cohort of 60 healthy controls, 63 individuals with prediabetes and 64 T2DM patients, the AUCs of hsa_circ_0054633 increased after adjusting for T2DM risk factors (0.841 for prediabetes; 0.773 to 0.910; p<0.001 and 0.834 for T2DM; 0.762 to 0.905; p<0.001).
At present, the oral glucose tolerance test (OGTT) is the gold standard for establishing a T2DM diagnosis. However, the procedure is only performed when there is a strong suspicion of T2DM, because OGTT is complicated and time-consuming. Other diagnostic methods also have drawbacks—with fasting plasma glucose presenting a risk of high missed diagnosis rate, and haemoglobin A1c not having been standardized in Chinese hospitals, researchers noted. [Pract Diabetes Int 2001;18:89–93]
Findings of the current study suggest that hsa_circ_0054633 has a potential diagnostic capability for prediabetes and T2DM, with the added advantage of simple testing using peripheral blood and of a relatively low cost and high specificity and sensitivity, they said.
A gene ontology analysis further support the role of hsa_circ_0054633 in prediabetes and T2DM diagnosis, having found that the biomarker “not only participates in biological processes, such as cell cycle and mitotic cell cycle arrest, but is strongly correlated with molecular catabolism,” they added.
“The proliferation of b cells is regulated by cell cycle progress, and decreased b-cell proliferation is the major cause of insufficient insulin secretion, which is the basic characteristic of T2DM,” they explained. “Besides, T2DM is a chronic metabolic disease characterized by disordered carbohydrate, lipid and protein metabolism, and we hypothesize that hsa_circ_0054633 may participate in the pathogenesis of T2DM by influencing the cellular metabolism and cell cycle.”
Researchers, however, acknowledged that the present study only validated hsa_circ_0054633, leaving the expression profiles of other circRNAs in T2DM and prediabetes patients unexplored. Additional studies are thus necessary to verify the current data in larger and more diverse cohorts, especially to determine whether populations in other regions exhibit similar circRNAs expression profiles.