鼻咽癌患者血浆纤维蛋白原水平与患者

预后及肿瘤转移的关系

doi:10.3760/cma.j.issn.1673-422X.2018.12.003

摘要/Abstract

摘要： 目的探讨鼻咽癌患者治疗前血浆纤维蛋白原水平与患者预后及肿瘤转移的相关性。方法收集2005年1月至2014年10月我院收治的817例非远处转移鼻咽癌患者的临床资料，并对患者进行随访，中位随访时间为37.6个月。通过受试者工作特征（ROC）曲线确定治疗前血浆纤维蛋白原的临界值。通过KaplanMeier方法和Cox回归模型分析患者总生存期（OS）和无远处转移生存期（DMFS）及其相关因素。结果通过ROC曲线分析确定治疗前血浆纤维蛋白原临界值为3.314 g/L。治疗前血浆纤维蛋白原水平与TNM分期（χ2=6.048，P=0.014）、T分期（χ2=13.764，P＜0.001）、治疗后远处转移（χ2=14.637，P<0.001）相关。生存分析结果显示，治疗前血浆纤维蛋白原水平≥3.314 g/L的患者3年OS率和3年DMFS率显著低于治疗前血浆纤维蛋白原＜3.314 g/L者，差异均有统计学意义（87.2%∶95.6%，χ2=4.562，P<0.001；71.1%∶82.2%，χ2=5.153，P<0.001）。Cox多因素分析结果显示，治疗前高水平血浆纤维蛋白原（HR=1.961，95%CI为1.332～2.917，P=0.001）、EB病毒DNA（HR=1.929，95%CI为1.275～2.849，P=0.001）和治疗前分期（HR=1.653，95%CI为1.013～2.709，P=0.045）是患者OS的独立影响因素；治疗前高水平血浆纤维蛋白原（HR=1.519，95%CI为1.142～1.964，P=0.002）和EB病毒DNA（HR=1.950，95%CI为1.483～2.555，P＜0.001）是患者DMFS的独立影响因素。817例患者中179例（21.91%）在随访期间发生了转移，其中159例（88.83%）在治疗后3年内发生转移。638例未发生转移的患者治疗前血浆纤维蛋白原水平（3.197±1.009）显著低于179例发生转移的患者（3.351±1.042；t=5.089，P=0.024），并且显著低于87例发生骨转移的患者（3.430±1.004；t=6.752，P=0.009）、68例发生肺转移的患者（3.301±1.018；t=4.281，P=0.039）及71例发生肝转移的患者（3.413±1.107；t=6.398，P=0.011）。结论治疗前血浆纤维蛋白原水平可作为评估鼻咽癌患者预后的独立指标，并且与肿瘤转移相关。

关键词: 纤维蛋白原, 鼻咽肿瘤, 肿瘤转移, 预后

Abstract: ObjectiveTo investigate the relationships between the plasma fibrinogen level before treatment and prognosis and tumor metastasis in patients with nasopharyngeal carcinoma. MethodsThe clinical data of 817 patients with nondistant metastasis nasopharyngeal carcinoma from January 2005 to October 2014 in our hospital were collected. All the patients were followed up, and the median followup time was 37.6 months. The critical value of plasma fibrinogen before treatment was determined by receiver operating characteristic (ROC) curve. The overall survival (OS) and distant metastasis free survival (DMFS) and their relevant factors were analyzed by KaplanMeier and Cox regression model. ResultsThe critical value of plasma fibrinogen before treatment was 3.314 g/L determined by ROC curve analysis. The plasma fibrinogen level before treatment was related to the TNM stage (χ2=6.048, P=0.014), T stage (χ2=13.764, P＜0.001) and distant metastasis after treatment (χ2=14.637, P<0.001). Survival analysis showed that the 3year OS rate and 3year DMFS rate in patients with plasma fibrinogen level ≥3.314 g/L before treatment were significantly lower than those in patients with plasma fibrinogen level ＜3.314 g/L, with significant differences (87.2% vs. 95.6%, χ2=4.562, P<0.001; 71.1% vs. 82.2%, χ2=5.153, P<0.001). Cox multivariate analysis showed that high level of plasma fibrinogen before treatment (HR=1.961, 95%CI: 1.3322.917, P=0.001), EB virus DNA (HR=1.929, 95%CI: 1.2752.849, P=0.001) and pretreatment stage (HR=1.653, 95%CI: 1.0132.709, P=0.045) were the independent influencing factors of OS. The high level of plasma fibrinogen before treatment (HR=1.519, 95%CI: 1.1421.964, P=0.002) and EB virus DNA (HR=1.950, 95%CI: 1.4832.555, P＜0.001) were the independent influencing factors of DMFS. Of the 817 patients, 179 patients (21.91%) had metastasis during the followup period, and 159 patients (88.83%) had metastasis within 3 years after treatment. The plasma fibrinogen level before treatment in 638 patients without metastasis (3.197±1.009) was significantly lower than that in 179 patients with metastasis (3.351±1.042; t=5.089, P=0.024), and was significantly lower than that in 87 patients with bone metastasis (3.430±1.004; t=6.752, P=0.009), 68 patients with pulmonary metastasis (3.301±1.018; t=4.281, P=0.039) and 71 patients with liver metastasis (3.413±1.107; t=6.398, P=0.011). ConclusionThe plasma fibrinogen level before treatment can be used as an independent index to predict the prognosis of patients with nasopharyngeal carcinoma, which is related to tumor metastasis.

Key words: Fibrinogen, Nasopharyngeal neoplasms, Metastasis, Prognosis

袁浩展,姬敏干,王艳婷. 鼻咽癌患者血浆纤维蛋白原水平与患者预后及肿瘤转移的关系[J]. 国际肿瘤学杂志, 2018, 45(12): 716-720.

Yuan Haozhan, Ji Mingan, Wang Yanting. Relationships between plasma fibrinogen and prognosis and tumor metastasis in patients with nasopharyngeal carcinoma[J]. Journal of International Oncology, 2018, 45(12): 716-720.

参考文献

［1］ Chen W, Zheng R, Zhang S, et al. Report of cancer incidence and mortality in China, 2010［J］. Ann Transl Med, 2014, 2(7): 61. DOI: 10.3978/j.issn.23055839.2014.04.05. ［2］ Huang TR, Zhang SW, Chen WQ, et al. Trends in nasopharyngeal carcinoma mortality in China, 19732005［J］. Asian Pac J Cancer Prev, 2012, 13(6): 24952502. ［3］ Xu ZJ, Zheng RS, Zhang SW, et al. Nasopharyngeal carcinoma incidence and mortality in China in 2009［J］. Chin J Cancer, 2013, 32(8): 453460. DOI: 10.5732/cjc.013.10118. ［4］ Cao SM, Simons MJ, Qian CN. The prevalence and prevention of nasopharyngeal carcinoma in China［J］. Chin J Cancer, 2011, 30(2): 114119. ［5］ Xu ZX, Lin ZX, Fang JY, et al. Mortality characteristic and prediction of nasopharyngeal carcinoma in China from 1991 to 2013［J］. Asian Pac J Cancer Prev, 2015, 16(15): 67296734. ［6］毛承刚, 万俐佳, 沈敏, 等. 鼻咽癌治疗后生存率和预后总结与分析［J］. 中国耳鼻咽喉颅底外科杂志, 2015, 21(5): 386389. DOI: 10.11798/j.issn.10071520.201505009. ［7］刘宇, 杨澎, 田晓波, 等. 胃癌患者肿瘤恶性程度与凝血功能的相关性研究［J］. 中国医学装备, 2017, 14(6): 8992. DOI: 10.3969/J.ISSN.16728270.2017.06.025. ［8］徐建华. 胃癌术后凝血功能对患者生存率的影响［J］. 基层医学论坛, 2012, 16(4): 450452. ［9］胥芸芸, 翟振兴, 李桂香. 血浆纤维蛋白表达水平与肾细胞癌风险相关性的Meta分析［J］. 中国循证医学杂志, 2017, 17(5): 529535. DOI: 10.7507/16722531.201606076. ［10］张礼, 燕锦. 血浆纤维蛋白原在结直肠癌中的研究进展［J］. 肿瘤预防与治疗, 2016, 29(4): 231234. DOI: 10.3969/j.issn.16740904.2016.04.009. ［11］韩宇, 赵隽. 血浆纤维蛋白原在恶性肿瘤中的研究进展［J］. 中国医学创新, 2013, 10(27): 162164. DOI: 10.3969/j.issn.16744985.2013.27.075. ［12］ Gooi Z, Fakhry C, Goldenberg D, et al. AHNS series: do you know your guidelines? Principles of radiation therapy for head and neck cancer: a review of the National Comprehensive Cancer Network guidelines［J］. Head Neck, 2016, 38(7): 987992. DOI: 10.1002/hed.24448. ［13］ Chen A, Lee N, Yang C, et al. Comparison of intensitymodulated radiotherapy using helical tomotherapy and segmental multileaf collimatorbased techniques for nasopharyngeal carcinoma: dosimetric analysis incorporating quality assurance guidelines from RTOG 0225［J］. Technol Cancer Res Treat, 2010, 9(3): 291298. DOI: 10.1177/153303461000900308. ［14］ Lan M, Chen C, Huang Y, et al. Elevated plasma fibrinogen level shows superior prognostic value than EpsteinBarr virus DNA load for stage ⅣA/B nasopharyngeal carcinoma patients in the intensitymodulated radiotherapy era［J］. Oncotarget, 2016, 7(29): 4624246252. DOI: 10.18632/oncotarget.10083. ［15］罗晚媛, 唐莹, 何本夫. 血浆EBVDNA表达水平与鼻咽癌分期的相关性分析［J］. 实用癌症杂志, 2015, 30(8): 11161118. DOI: 10.3969/j.issn.10015930.2015.08.003. ［16］盖秀娟, 魏玉梅, 李宝生. 鼻咽癌预后相关因素研究进展［J］. 中华肿瘤防治杂志, 2016， 23(20): 13981402. DOI:10.16073/j.cnki.cjcpt.2016.20.011. ［17］ Pichler M, Hutterer GC, Stojakovic T, et al. High plasma fibrinogen level represents an independent negative prognostic factor regarding cancerspecific, metastasisfree, as well as overall survival in a European cohort of nonmetastatic renal cell carcinoma patients［J］. Br J Cancer, 2013, 109(5): 11231129. DOI: 10.1038/bjc.2013.443. ［18］韩晓娜, 孙振强, 唐勇, 等. 结肠癌术前血浆纤维蛋白原水平与临床病理特征的关系［J］. 肿瘤防治研究, 2014, 41(12): 13261329. DOI: 10.3971/j.issn.10008578.2014.12.016. ［19］ Gao J, Zhang HY, Xia YF. Increased platelet count is an indicator of metastasis in patients with nasopharyngeal carcinoma［J］. Tumour Biol, 2013, 34(1): 3945. DOI: 10.1007/s132770120508y.

[1]	钱晓涛, 石子宜, 胡格, 吴晓维. Ⅲ~ⅣA期食管鳞状细胞癌放化疗后行巩固化疗的疗效：一项真实世界临床研究[J]. 国际肿瘤学杂志, 2024, 51(6): 326-331.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[4]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[5]	范志鹏, 余静, 胡静, 廖正凯, 徐禹, 欧阳雯, 谢丛华. 炎症标志物的变化趋势对一线接受免疫联合化疗的晚期非小细胞肺癌患者预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(5): 257-266.
[6]	杨琳, 路宁, 温华, 张明鑫, 朱琳. 炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[7]	刘萍萍, 何学芳, 张翼, 杨旭, 张珊珊, 季一飞. 原发性脑胶质瘤患者术后复发危险因素及预测模型构建[J]. 国际肿瘤学杂志, 2024, 51(4): 193-197.
[8]	万芳, 杨钢, 李睿, 万启晶. 食管癌患者血清miR-497、miR-383水平及临床意义[J]. 国际肿瘤学杂志, 2024, 51(4): 204-209.
[9]	姚益新, 沈煜霖. 血清SOCS3、TXNIP水平对肝细胞癌TACE治疗预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(4): 217-222.
[10]	孙维蔚, 姚学敏, 王鹏健, 王静, 贾敬好. 基于血液学指标探讨免疫治疗晚期非小细胞肺癌预后因素及列线图构建[J]. 国际肿瘤学杂志, 2024, 51(3): 143-150.
[11]	李书月, 马辰莺, 周菊英, 徐晓婷, 秦颂兵. 寡转移非小细胞肺癌的放疗进展[J]. 国际肿瘤学杂志, 2024, 51(3): 170-174.
[12]	刘玉兰, 井海燕, 孙静, 宋伟, 沙丹. 胃癌免疫治疗疗效预测及预后标志物的研究进展[J]. 国际肿瘤学杂志, 2024, 51(3): 175-180.
[13]	彭琴, 蔡玉婷, 王伟. KPNA2在肝癌中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(3): 181-185.
[14]	孙国宝, 杨倩, 庄庆春, 高斌斌, 孙晓刚, 宋伟, 沙丹. 结直肠癌肝转移组织病理学生长方式研究进展[J]. 国际肿瘤学杂志, 2024, 51(2): 114-118.
[15]	陈波光, 王苏贵, 张永杰. 血清胆碱酯酶与炎症标志物在ⅠA~ⅢA期乳腺癌预后中的作用[J]. 国际肿瘤学杂志, 2024, 51(2): 73-82.