Department of Pathology, The Royal Hobart Hospital, Tasmania, Australia
Department of Biochemistry, Sinha Institute of Medical Science and Technology, Kolkata, India.
Biosci Rep. 2019 Jul 29;39(7). doi: 10.1042/BSR20182313. Print 2019 Jul 31.
Lack of insulin or insulin resistance (IR) plays a central role in diabetes mellitus and makes diabetics prone to acute ischemic heart disease (AIHD). It has likewise been found that many cancer patients, including prostate cancer patients die of AIHD. Previously it has been delineated from our laboratory that dermcidin could induce anomalous platelet aggregation in AIHD and also impaired nitric oxide and insulin activity and furthermore dermcidin was also found in a few types of cancer patients. To determine the role of this protein in prostatic malignancy, a retrospective case-control study was conducted and blood was collected from prostate cancer patients and healthy normal volunteers. So, we measured the level of dermcidin protein and analyzed the IR by Homeostasis Model Assessment (HOMA) score calculation. Nitric oxide was measured by methemoglobin method. HDL, glycated hemoglobin (HbA1c), BMI, hs-cTroponin-T were measured for the validation of the patients' status in the presence of Dermcidin isoform-2 (DCN-2). Multiple logistic regression model adjusted for age and BMI identified that the HOMA score was significantly elevated in prostate cancer patients (OR = 7.19, <0.001). Prostate cancer patients are associated with lower level of NO and higher level of both proteins dermcidin (OR = 1.12, <0.001) and hs-TroponinT (OR = 1.76, <0.001). From the results, it can be interpreted that IR plays a key role in the pathophysiology of prostate cancer where dermcidin was the cause of IR through NO inhibition leading to AIHD was also explained by high-sensitive fifth generation cTroponin-T (hs-cTroponinT) and HbA1c level which are associated with endothelial dysfunction.
胰岛素缺乏或胰岛素抵抗（IR）在糖尿病中起着核心作用，使糖尿病患者容易发生急性缺血性心脏病（AIHD）。同样，已经发现许多癌症患者，包括前列腺癌患者，死于 AIHD。以前，我们实验室已经从我们的实验室中得出结论，dermcidin 可以在 AIHD 中诱导异常的血小板聚集，并且还会损害一氧化氮和胰岛素的活性，此外，还在一些类型的癌症患者中发现了 dermcidin。为了确定这种蛋白质在前列腺恶性肿瘤中的作用，进行了一项回顾性病例对照研究，并从前列腺癌患者和健康正常志愿者中采集了血液。因此，我们测量了 dermcidin 蛋白的水平，并通过稳态模型评估（HOMA）评分计算分析了 IR。通过高铁血红蛋白法测量了一氧化氮。为了验证 Dermcidin 同工型-2（DCN-2）存在时患者的状态，还测量了 HDL、糖化血红蛋白（HbA1c）、BMI、hs-cTroponin-T。多元逻辑回归模型调整了年龄和 BMI，发现前列腺癌患者的 HOMA 评分显着升高（OR = 7.19，<0.001）。前列腺癌患者与较低水平的 NO 和较高水平的两种蛋白 dermcidin（OR = 1.12，<0.001）和 hs-TroponinT（OR = 1.76，<0.001）相关。从结果可以解释，IR 在前列腺癌的病理生理学中起着关键作用，其中 dermcidin 通过抑制 NO 导致 IR，这也可以通过高敏第五代 cTroponin-T（hs-cTroponinT）和与内皮功能障碍相关的 HbA1c 水平来解释。
