Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy.
Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.
Int J Mol Sci. 2022 Jul 25;23(15):8198. doi: 10.3390/ijms23158198.
Type 2 diabetes and renal damage are strictly linked. The progressive increase in T2D incidence has stimulated the interest in novel biomarkers to improve the diagnostic performance of the commonly utilized markers such as albuminuria and eGFR. Through microarray method, we analyzed the entire transcriptome expressed in 12 serum samples of diabetic patients, six without DKD and six with DKD; the downregulation of the most dysregulated transcripts was validated in a wider cohort of 69 patients by qPCRs. We identified a total of 33 downregulated transcripts. The downregulation of four mitochondrial messenger RNAs (MT-ATP6, MT-ATP8, MT-COX3, MT-ND1) and other two transcripts (seysnoy, skerdo) was validated in patients with eGFR stage G3 versus G2 and G1. The four messenger RNAs correlated with creatinine and eGFR stages, while seysnoy and skerdo were associated with white blood cell values. All transcripts correlated also with Blood Urea Nitrogen. The four mitochondrial messenger RNAs had a high diagnostic performance in G3 versus G2 discrimination, with AUC values above 0.8. The most performant transcript was MT-ATP6, with an AUC of 0.846; sensitivity = 90%, specificity = 76%, -value = 7.8 × 10. This study led to the identification of a specific molecular signature of DKD, proposing the dosage of RNAs, especially mitochondrial RNAs, as noninvasive biomarkers of diabetes complication.
2 型糖尿病与肾脏损害密切相关。2 型糖尿病发病率的不断增加，激发了人们对新型生物标志物的兴趣，以期提高白蛋白尿和 eGFR 等常用标志物的诊断性能。我们通过微阵列方法分析了 12 例糖尿病患者血清样本中表达的全转录组，其中 6 例无 DKD，6 例有 DKD；通过 qPCR 在更大的 69 例患者队列中验证了最失调转录本的下调。我们共鉴定出 33 个下调的转录本。四个线粒体信使 RNA（MT-ATP6、MT-ATP8、MT-COX3、MT-ND1）和其他两个转录本（sey snoy、skerdo）的下调在 eGFR 分期 G3 与 G2 和 G1 的患者中得到了验证。这四个信使 RNA 与肌酐和 eGFR 分期相关，而 seysnoy 和 skerdo 与白细胞值相关。所有转录本也与血尿素氮相关。这四个线粒体信使 RNA 在 G3 与 G2 区分中的诊断性能较高，AUC 值均高于 0.8。表现最佳的转录本是 MT-ATP6，AUC 为 0.846；灵敏度=90%，特异性=76%，-值=7.8×10。本研究确定了 DKD 的特定分子特征，提出了 RNA（特别是线粒体 RNA）剂量作为糖尿病并发症的非侵入性生物标志物。
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