结合炎性细胞因子构建原发性肝癌术后复发的Nomogram模型

高素华; 甘洪颖; 王君

doi:10.3969/j.issn.1001-5256.2019.07.020

结合炎性细胞因子构建原发性肝癌术后复发的Nomogram模型

DOI: 10.3969/j.issn.1001-5256.2019.07.020

华中科技大学同济医学院附属武汉中心医院

基金项目:

武汉市教育厅科研项目(D20162102)；

详细信息

中图分类号: R735.7
计量
- 文章访问数: 1289
- HTML全文浏览量: 22
- PDF下载量: 267
- 被引次数: 0
出版历程
- 收稿日期: 2019-02-28
- 出版日期: 2019-07-20

Establishment of Nomogram model of postoperative recurrence of primary hepatocellular carcinoma with reference to inflammatory cytokines

Wuhan Central Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology

Research funding:

摘要

摘要: 目的收集临床指标及相关炎性细胞因子数据,构建肝细胞癌（HCC）术后复发的Nomogram模型。方法选取2014年1月～2016年1月在武汉中心医院行首次行肝切除术治疗的314例HCC患者,根据随访结果分为无复发组与复发组。收集患者一般资料,检测肝功能及炎性细胞因子水平。计数资料2组间比较采用χ2检验,等级资料2组间比较采用Mann-Whitney U检验。采用受试者工作特征曲线（ROC曲线）获得计量资料的最佳截断值。复发的独立危险因素采用多因素Cox比例风险模型分析;根据多因素Cox比例风险模型的结果构建Nomogram模型,进行内部数据验证并计算一致性指数（C-index）。结果术后随访1～40个月,中位随访期13个月,无复发患者140例,复发患者174例,中位无复发生存期为19个月,半年无复发生存率68. 2%,1年无复发生存率57. 3%,2年无复发生存率45. 9%。复发组患者的年龄、肿瘤最大直径、BMI、IL-2、IL-6、IL-8、IL-17、NLR、TNFα、CRP、ALT、AST、TBil与无复发组比较,差异均有统计学意义（P值均<0. 05）。Cox模型分析结果...
- 癌,肝细胞 /
- 肝切除术 /
- 复发 /
- 残线图
Abstract: Objective To establish the Nomogram model of postoperative recurrence of hepatocellular carcinoma ( HCC) by collecting the data on clinical indices and inflammatory cytokines. Methods A total of 314 patients with HCC who were admitted to Wuhan Central Hospital from January 2014 to January 2016 and underwent hepatectomy for the first time were enrolled, and according to follow-up results, these patients were divided into non-recurrence group and recurrence group. General data were collected, and liver function parameters and inflammatory cytokines were measured. The chi-square test was used for comparison of categorical data between two groups, and the Mann-Whitney U test was used for comparison of ranked data between two groups. The receiver operating characteristic ( ROC) curve was used to obtain the optimal cut-off values of continuous data. The multivariate Cox proportional hazards model was used to investigate the independent risk factors for recurrence. The Nomogram model was established according to the results of the multivariate Cox proportional hazards model and was validated by internal data, and the consistency index ( C-index) was calculated. Results The follow-up time ranged from1 month to 40 months, with a median follow-up time of 13 months. Of all patients, 140 had no recurrence, and 174 experienced recurrence. The median recurrence-free survival time was 19 months, and the half-, 1-, and 2-year recurrence-free survival rates were68. 2%, 57. 3%, and 45. 9%, respectively. There were significant differences between the two groups in age, maximum tumor diameter, body mass index ( BMI) , interleukin-2, interleukin-6, interleukin-8, interleukin-17 ( IL-17) , neutrophil-lymphocyte ratio, tumor necrosis factor α ( TNF α) , C-reactive protein, alanine aminotransferase ( ALT) , aspartate aminotransferase, and total bilirubin ( TBil) ( all P < 0. 05) . The Cox proportional hazards model showed that age > 63 years ( hazard ratio[HR]= 2. 391, P < 0. 05) , maximum tumor diameter > 6 cm ( HR = 1. 851, P < 0. 05) , BMI > 27. 17 kg/m2 ( HR = 1. 546, P < 0. 05) , IL-17 > 10. 8 pg/m L ( HR = 1. 556, P <0. 05) , TNF α > 11. 8 ng/L ( HR = 1. 562, P < 0. 05) , ALT > 42 U/L ( HR = 1. 624, P < 0. 05) , and TBil > 15. 6 μmol/L ( HR = 1. 534, P < 0. 05) were independent risk factors for postoperative recurrence in patients with HCC. Validation by internal data showed a C-index of0. 724 ( 95% confidence interval: 0. 668-0. 824) . Conclusion The Nomogram model established in this study can accurately predict the recurrence of HCC patients after first-time hepatectomy, but more clinical studies are needed to confirm this result.
- carcinoma, hepatocellular /
- hepatectomy /
- recurrence /
- nomograms

HTML全文

参考文献(22)

[1]FERLAY J, SOERJOMATARAM I, DIKSHIT R, et al.Cancer incidence and mortality worldwide:Sources, methods and major patterns in GLOBOCAN 2012[J].Int J Cancer, 2015, 136 (5) :359-386.

[2] YAMASAKI S, HASEGAWA H, MAKUUCHI M, et al.Choice of treatments for small hepatocellular carcinoma:Hepatectomy, embolization or ethanol injection[J].J Gastroenterol, 2010, 6 (4) :408-413.

[3] POON RP, FAN ST, NG OL, et al.Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma[J].Cancer, 2000, 89 (3) :500-507.

[4]POON RP, FAN ST, NG OL, et al.Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function:Implications for a strategy of salvage transplantation[J].Ann Surg, 2002, 235 (3) :373-382.

[5]GRIVENNIKOV SI, GRETEN FR, KARIN M.Immunity, inflammation, and cancer[J].Mol Biol Cell, 2010, 140 (6) :833-899.

[6] Liver Surgery Group, Surgical Society of Chinese Medical Association.Expert consensus on selection of surgical treatments for hepatocellular carcinoma (2016 3rd edition) [J].Chin JDig Surg, 2017, 16 (2) :113-115. (in Chinese) 中华医学会外科学分会肝脏外科学组.肝细胞癌外科治疗方法的选择专家共识 (2016年第3次修订) [J].中华消化外科杂志, 2017, 16 (2) :113-115.

[7]YANG Z, WANG JL, SHANG RZ, et al.Correlation between preoperative serum alpha-fetoprotein (AFP) level and early recurrence of patients the hepatocellular carcinoma after partial hepatectomy[J].Chin J Hepatobiliary Surg, 2018, 24 (3) :179-183. (in Chinese) 杨针, 汪建林, 尚润泽, 等.术前血清甲胎蛋白水平与肝细胞癌术后患者早期复发的相关性分析[J].中华肝胆外科杂志, 2018, 24 (3) :179-183.

[8] JUNG SM, KIM JM, CHOI GS, et al.Characteristics of early recurrence after curative liver resection for solitary hepatocellular carcinoma[J].J Gastrointest Surg, 2019, 23 (2) :304-311.

[9]TANAKA S, LIMURO Y, HIRANO T, et al.Safety of hepatic resection for hepatocellular carcinoma in obese patients with cirrhosis[J].Surg Today, 2013, 43 (11) :1290-1297.

[10] NISHIKAWA H, OSAKI Y, TAKEDA H, et al.Effect of body mass index on survival after curative therapy for non-B nonC hepatocellular carcinoma[J].Chin J Cancer, 2013, 22 (2) :173-181.

[11]TIAN J, MENG QH, LIANG QY, et al.Research progress in the associations of metabolic diseases and therapeutic drugs with hepatocellular carcinomas[J].Chin J Clin Pharmacol Ther, 2019, 24 (1) :103-110. (in Chinese) 田婧, 蒙秋华, 梁秋云, 等.代谢性疾病及治疗药物与肝癌的相关性研究进展[J].中国临床药理学与治疗学, 2019, 24 (1) :103-110.

[12] LORINCZ MA.Molecular links between obesity and breast cancer[J].Endocr Relat Cancer, 2006, 13 (2) :279-292.

[13]WANG XJ, YUAN SL, LU Q, et al.Potential involvement of leptin in carcinogenesis of hepatocellular carcinoma[J].World J Gastroenterol, 2004, 10 (17) :2478-2481.

[14]DENG WW, ZHU WM, YI C, et al.Association of serum interleukin-17 level with early recurrence and prognosis after radical surgery in hepatocellular carcinoma patients with differentlevels of alpha-fetoprotein[J].J Clin Hepatol, 2018, 34 (2) :298-302. (in Chinese) 邓伟伟, 朱文明, 易超, 等.不同AFP水平下血清IL-1与肝癌根治术后早期复发和预后的关系[J].临床肝胆病杂志, 2018, 34 (2) :298-302.

[15]TU JF, PAN HY, YING XH, et al.Mast cells comprise the major of interleukin 17-producing cells and predict a poor prognosis in hepatocellular carcinoma[J].Medicine (Baltimore) , 2016, 95 (13) :e3220.

[16]AZZAZENE D, AL THAWADI H, AL FARSI H, et al.Plasma endothelial protein C receptor influences innate immune response in ovarian cancer by decreasing the population of natural killer and TH17 helper cells[J].Int J Oncol, 2013, 43 (4) :1011-1018.

[17]ZHAGN JH, ZHENG C, ZHOU ZH, et al.Research progress of relationship the between immune cells and hepatocellular carcinoma[J].China Med Herald, 2018, 15 (36) :24-27. (in Chinese) 张景豪, 郑超, 周振华, 等.免疫细胞与肝细胞癌关系的研究进展[J].中国医药导报, 2018, 15 (36) :24-27.

[18] FRANCK H, ABBY G, ERIK TO, et al.Interleukin-17 and type 17 helper T cells in cancer management and research[J].Immunotargets Ther, 2014, 10 (3) :39-54.

[19] HU Z, LUO D, WANG D, et al.IL-17 activates the IL-6/STAT3 signal pathway in the proliferation of hepatitis B virusrelated hepatocellular carcinoma[J].Cell Physiol Biochem, 2017, 43 (6) :2379-2390.

[20]BALACHANDRAN VP, GONEN M, SMITH JJ, et al.Nomograms in oncology:More than meets the eye[J].Lancet Oncol, 2015, 16 (4) :173-180.

[21]TAN W, LUO X, LI W, et al.TNF-αis a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma[J].EBio Medicine, 2018, 40:446-456.

[22]AYUBI E, SAFIRI S.Nomogram predicting long-term survival after the diagnosis of intrahepatic recurrence of hepatocellular carcinoma following an initial liver resection:Methodological issues[J].Int J Clin Oncol, 2017, 22 (4) :715-725.

施引文献

资源附件(0)

访问统计