Yu Qian, Zhang Zhong, Zhang Haijun
Department of Gastroenterology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People's Republic of China.
Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People's Republic of China.
Cancer Manag Res. 2021 Feb 11;13:1291-1298. doi: 10.2147/CMAR.S293473. eCollection 2021.
Pancreatic cancer (PC), a devastating cancer worldwide, remains dismal prognosis due to its clinical elusiveness, especially in relation to diabetes mellitus (DM). The study aims to investigate the effect of glucose variability on COL6A1 in PC cancer cells and the prognostic potential of COL6A1 for PC patient associated with DM.
After PC cancer cell lines of AsPC-1 and BxPC-3 were treated with hyperglycemia and hypoglycemia, Giemsa staining and Transwell chamber were performed to assay plate clone formation, migration and invasion. Expressions of COL6A1 of PC cancer cell lines under different extracellular glucose levels were detected by qRT-PCR and Western blotting. The level of COL6A1 expression in PC patients with/without DM was further observed with immunohistochemistry. The prognostic impact of COL6A1 on PC patients with DM was assessed by Kaplan-Meier survival curve analysis.
Hyperglycemia promoted proliferation, migration and invasion of PC cancer cells compared with hypoglycemia. Glucose variability could regulate expression of COL6A1 in PC cancer cells, both mRNA and COL6A1 protein upregulated in cancer cells cultured with hyperglycemic than that with hypoglycemic. The level of COL6A1 expression was higher in PC patients with DM than that without DM. Besides, COL6A1 was significantly associated with the clinical prognosis of PC patients with DM, higher COL6A1 leading to lower overall survival (OS).
Glucose variability had effect on PC cancer cells through regulation of COL6A1. Accordingly, COL6A1 was associated with poorer prognosis in PC patients with DM.
胰腺癌（PC）是一种在全球范围内具有毁灭性的癌症，由于其临床隐匿性，尤其是与糖尿病（DM）相关时，预后仍然很差。本研究旨在探讨血糖变异性对PC癌细胞中COL6A1的影响以及COL6A1对合并DM的PC患者的预后潜力。
对AsPC-1和BxPC-3两种PC癌细胞系进行高血糖和低血糖处理后，采用吉姆萨染色和Transwell小室检测平板克隆形成、迁移和侵袭能力。通过qRT-PCR和蛋白质免疫印迹法检测不同细胞外葡萄糖水平下PC癌细胞系中COL6A1的表达。采用免疫组织化学进一步观察合并/未合并DM的PC患者中COL6A1的表达水平。通过Kaplan-Meier生存曲线分析评估COL6A1对合并DM的PC患者的预后影响。
与低血糖相比，高血糖促进了PC癌细胞的增殖、迁移和侵袭。血糖变异性可调节PC癌细胞中COL6A1的表达，与低糖培养的癌细胞相比，高糖培养的癌细胞中mRNA和COL6A1蛋白均上调。合并DM的PC患者中COL6A1的表达水平高于未合并DM的患者。此外，COL6A1与合并DM的PC患者的临床预后显著相关，COL6A1水平越高，总生存期（OS）越低。
血糖变异性通过调节COL6A1对PC癌细胞产生影响。因此，COL6A1与合并DM的PC患者较差的预后相关。
