Sauriasari Rani, Sekar Andisyah Putri, Aisyah Nurul, Syahdi Rezi Riadhi, Matsuura Eiji
Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Neutron Therapy Research Center, Collaborative Research Center for OMIC & Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Diabetes Metab Syndr Obes. 2020 Feb 11;13:325-331. doi: 10.2147/DMSO.S213731. eCollection 2020.
Abnormalities in glucose metabolism in diabetic patients may lead to an increased risk of certain cancers. Epidemiological studies and meta-analysis have shown that factors such as gender, age, obesity, and insulin resistance are related to cancer incidence. The anti-p53 antibody is a known cancer marker due to tumor-associated p53 accumulation. Many studies have aimed to unravel the link between diabetes and cancer. Here, we aimed to elucidate the impact of diabetes on malignancies by analyzing anti-p53 antibody in sera of type 2 diabetes mellitus (T2DM) patients.
We conducted an observational study with a cross-sectional design. A total of 149 subjects comprised of 78 T2DM patients (32 with cancer risk and 46 subjects without cancer risk), 51 T2DM patients with cancer, and 20 healthy subjects as controls from multisites. The anti-p53 antibody was measured by enzyme-linked immunosorbent assay, while HbA1c was measured using the NGSP standardized method.
We observed an 8.3-fold (<0.05) increase of anti-p53 antibody in the sera of T2DM patients and a 24-fold increase (<0.001) in T2DM patients with cancer compared to healthy subjects. The anti-p53 antibodies significantly increased almost three times (<0.05) in T2DM patients with cancer (0.72 U/mL±0.20) compared to T2DM patients (0.25 U/mL±0.05). Meanwhile, this antibody was almost undetectable in healthy subjects as a control group (0.03 U/mL±0.03). The anti-p53 antibody level was higher in T2DM with cancer risk patients. However, we did not find a significant difference for it in T2DM without cancer risk patients (0.19 U/mL±0.03) and T2DM with cancer risk patients (0.29 U/mL±0.08). Multivariate regression analysis showed that T2DM with cancer was the only one independent factor (beta=0.218, =0.019) that could predict the increase of anti-p53 antibody, controlled by age, gender, BMI, DM duration, and HbA1c.
Our results showed that anti-p53 antibody almost not detected in healthy subjects, but 8.3-fold increase in the sera of T2DM patients and 24-fold increase in T2DM patients with cancer. Therefore, this biomarker provides new information which explains the link between diabetes and cancer.
糖尿病患者葡萄糖代谢异常可能导致某些癌症风险增加。流行病学研究和荟萃分析表明，性别、年龄、肥胖和胰岛素抵抗等因素与癌症发病率相关。抗p53抗体是一种已知的癌症标志物，因为肿瘤相关的p53会积累。许多研究旨在揭示糖尿病与癌症之间的联系。在此，我们旨在通过分析2型糖尿病（T2DM）患者血清中的抗p53抗体来阐明糖尿病对恶性肿瘤的影响。
材料与方法：我们进行了一项横断面设计的观察性研究。共有149名受试者，包括78名T2DM患者（32名有癌症风险，46名无癌症风险）、51名患有癌症的T2DM患者以及20名健康受试者作为多地点对照。通过酶联免疫吸附测定法测量抗p53抗体，而使用NGSP标准化方法测量糖化血红蛋白（HbA1c）。
结果：我们观察到，与健康受试者相比，T2DM患者血清中的抗p53抗体增加了8.3倍（<0.05），患有癌症的T2DM患者增加了24倍（<0.001）。与T2DM患者（0.25 U/mL±0.05）相比，患有癌症的T2DM患者的抗p53抗体显著增加了近三倍（<0.05）（0.72 U/mL±0.20）。同时，作为对照组的健康受试者中几乎检测不到这种抗体（0.03 U/mL±0.03）。有癌症风险的T2DM患者的抗p53抗体水平更高。然而，我们发现无癌症风险的T2DM患者（0.19 U/mL±0.03）和有癌症风险的T2DM患者（0.29 U/mL±0.08）之间没有显著差异。多变量回归分析表明，患有癌症的T2DM是唯一能够预测抗p53抗体增加的独立因素（β=0.218，P=0.019），该分析受年龄、性别、体重指数、糖尿病病程和糖化血红蛋白控制。
我们的结果表明，健康受试者中几乎检测不到抗p53抗体，但T2DM患者血清中增加了8.3倍，患有癌症的T2DM患者增加了24倍。因此，这种生物标志物提供了新的信息，解释了糖尿病与癌症之间的联系。
