糖尿病状态和胰岛素使用对肺癌预后的影响

发布时间：2018-04-19 15:04

本文选题：肺癌 + 糖尿病　；参考：《山东大学》2017年硕士论文

【摘要】：目的:本研究目的是评价糖尿病状态和胰岛素使用对肺癌患者生存的影响,并探讨其可能的机制。材料及方法:我们回顾性的分析了自2010年1月至2010年12月期间在山东省立医院胸外科进行肺癌切除手术的301例病人,收集其临床病理资料和随访数据,研究糖尿病状态和胰岛素使用情况对肺癌患者的总生存期和无进展生存期的影响。另外,我们还进行了体外细胞实验,初步研究胰岛素对肺癌细胞的影响。我们对有无胰岛素刺激的两组细胞在不同的时间点用MTT方法进行检测细胞增殖能力。用Hochest33258染色观察胰岛素对肺癌细胞凋亡的影响。我们还进行western blotting实验来检测胰岛素对IGF-1R信号通路的影响。糖尿病和胰岛素与肺癌患者临床病理特征的关系用卡方检验来评估,肺癌病人的生存情况用绘制生存曲线和COX风险模型来评估。所有统计检验为双边检验,统计分析所用软件为SPSS 20.0。结果:这301例肺癌患者中最终有296例患者纳入研究,有33例肺癌患者同时患有糖尿病,其中有13人使用了胰岛素治疗。通过对纳入研究的患者研究,我们发现患有糖尿病的肺癌病人比非糖尿病的肺癌病人预后要差,总生存期(p=0.002),无进展生存期(p=0.015)。使用胰岛素的肺癌病人比不使用胰岛素的肺癌病人预后要差,总生存期(p=0.004),无进展生存期(p=0.002)。多变量COX回归分析中,我们同样发现患有糖尿病的肺癌病人比非糖尿病的肺癌病人预后要差,总生存期(HR 2.235,95%CI 1.338-3.733,P0.001),无进展生存期(HR 1.931,95%CI 1.107-3.366,P=0.020);使用胰岛素的肺癌病人比不使用胰岛素的肺癌病人预后要差,总生存期(HR 2.996,95%CI 1.438-6.243,P=0.003),无进展生存期(HR 2.946,95%CI 1.416-6.131,P=0.004)。细胞实验发现胰岛素对肺癌细胞的增殖有促进作用但对其凋亡没有明显作用,胰岛素对肺癌细胞的胰岛素样生长因子受体(IGF-1R)信号通路有交叉激活的作用。结论:与单一患肺癌的病人相比,同时患有糖尿病的肺癌患者有较差的预后,使用胰岛素的患者也同样有较差的预后。通过细胞实验,我们认为高胰岛素血症可能是糖尿病导致肺癌患者生存期变短的原因之一。胰岛素通过交叉作用激活IGF-1R信号通路,从而影响肺癌细胞的增殖能力,进而影响肺癌患者的生存。本项研究提示应该采取措施改善该类肺癌患者体内高胰岛素对肺癌细胞的影响,进而改善该类肺癌患者的生存情况。考虑到该研究的局限性,在今后还需要更完善的前瞻性研究和随机临床试验来验证该实验结果。
[Abstract]:Objective: to evaluate the effects of diabetes and insulin use on the survival of lung cancer patients and explore its possible mechanism.Materials and methods: we retrospectively analyzed 301 patients undergoing lung cancer resection in thoracic surgery department of Shandong Provincial Hospital from January 2010 to December 2010, and collected their clinicopathological data and follow-up data.To study the effect of diabetes status and insulin use on the overall survival and progression free survival of lung cancer patients.In addition, we also carried out in vitro cell experiments to study the effect of insulin on lung cancer cells.We measured the proliferative ability of two groups of cells with or without insulin stimulation by MTT method at different time points.The effect of insulin on apoptosis of lung cancer cells was observed by Hochest33258 staining.We also performed western blotting tests to detect the effect of insulin on the IGF-1R signaling pathway.The relationship between diabetes and insulin and clinicopathological characteristics of lung cancer patients was evaluated by chi-square test, and survival status of lung cancer patients was assessed by drawing survival curve and COX risk model.All statistical tests are bilateral tests, and the software used for statistical analysis is SPSS 20.0.Results: of the 301 lung cancer patients, 296 were included in the study, 33 with diabetes and 13 with insulin therapy.In the study, we found that the prognosis of lung cancer patients with diabetes is worse than that of non-diabetic lung cancer patients, the total survival time is 0.002%, and the progression free survival time is 0.015%.The prognosis of patients with lung cancer treated with insulin was worse than that with lung cancer without insulin. The total survival time was 0. 004%, and the progression free survival time was 0. 002%.In multivariate COX regression analysis, we also found that the prognosis of lung cancer patients with diabetes was worse than that of non-diabetic lung cancer patients.Cell experiments showed that insulin could promote the proliferation of lung cancer cells but had no obvious effect on apoptosis. Insulin had a cross-activation effect on insulin-like growth factor receptor IGF-1R signaling pathway in lung cancer cells.Conclusion: compared with patients with single lung cancer, lung cancer patients with diabetes have poor prognosis, and patients with insulin also have poor prognosis.We believe that hyperinsulinemia may be one of the causes of shorter survival time in patients with lung cancer.Insulin activates the IGF-1R signaling pathway by cross-acting, which affects the proliferation of lung cancer cells and the survival of lung cancer patients.This study suggests that measures should be taken to improve the effect of hyperinsulinemia on lung cancer cells and thus to improve the survival of patients with this type of lung cancer.In view of the limitations of this study, more comprehensive prospective studies and randomized clinical trials are needed in the future to verify the results of the study.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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