Association of GAS6, AXL, and GAS6-AS lncRNAs with nephropathy in Egyptian patients with type 2 diabetes mellitus: a case-control observational study.

BACKGROUND/OBJECTIVES: Diabetic nephropathy (DN) is a prevalent microvascular diabetic complication that is not totally unveiled. In this study, we considered GAS6, AXL, GAS6-AS1, and GAS6-DT as possible early diagnostic biomarkers of DN.

SUBJECTS/METHODS: The study included 70 patients with normoalbuminuria type 2 diabetes (DM), 70 patients with microalbuminuria type 2 diabetes (DN), and 60 apparently healthy controls. Fasting plasma glucose, glycosylated hemoglobin, and plasma creatinine were enzymatically assayed. Albuminuria, plasma GAS6, and AXL levels were determined using ELISA. Long non-coding RNAs GAS6-AS1 and GAS6-DT levels were determined in blood using qRT-PCR. Several bioinformatics databases were employed to suggest interactions with the studied biomolecules.

RESULTS: GAS6 and AXL were downregulated in DM + DN compared to controls, being the lowest in DN (p < 0.0001). GAS6-DT was upregulated in DM + DN compared to controls, being the highest in DN (p < 0.0001). GAS6-AS1 was higher in DN than in controls (p = 0.013). GAS6, AXL, and GAS6-DT showed fair-to-moderate significant correlations with HbA1c, fasting glucose, creatinine, and albuminuria. ROC curves showed remarkable diagnostic power of GAS6, AXL, and GAS6-DT (AUC = 0.72-1.0), but not GAS6-AS1, in DN and DM, with moderate-to-excellent agreement with conventional diagnostics.

CONCLUSIONS: The current findings emphasize the significance of the GAS6/AXL pathway in DM and DN progression, where GAS6, AXL, and GAS6-DT showed significantly altered values in DM, and further in DN, with notable diagnostic power for both diseases. To date, this is the first study confirming the diagnostic power of AXL and GAS6-DT in DN and DM. Future studies are warranted to evaluate therapeutically targeting this pathway to manage DN.