切换至 "中华医学电子期刊资源库"
高级检索
中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2024, Vol. 13 ›› Issue (06) : 825 -830. doi: 10.3877/cma.j.issn.2095-3232.2024985

临床研究

血GP73水平在原发性肝癌TACE疗效评价中的作用
李一帆1, 朱帝文1, 任伟新1,†(), 鲍应军1, 顾俊鹏1, 张海潇1, 曹耿飞1, 阿斯哈尔·哈斯木1, 纪卫政1   
  1. 1.830011 乌鲁木齐，新疆医科大学第一附属医院介入放射科
  • 收稿日期:2024-07-24 出版日期:2024-12-10
  • 通信作者: 任伟新
  • 基金资助:
    国家自然科学基金（82060334）新疆维吾尔自治区自然科学基金重点项目（2021D01D22）新疆维吾尔自治区第二批“天池英才”青年博士引进计划项目

Role of serum GP73 level in the evaluation of TACE efficacy for primary liver cancer

Yifan Li1, Diwen Zhu1, Weixin Ren1,†(), Yingjun Bao1, Junpeng Gu1, Haixiao Zhang1, Gengfei Cao1, Weizheng Ji1   

  1. 1.Department of Interventional Radiology，the First Affiliated Hospital of Xinjiang Medical University，Urumqi 830011，China
  • Received:2024-07-24 Published:2024-12-10
  • Corresponding author: Weixin Ren
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

李一帆, 朱帝文, 任伟新, 鲍应军, 顾俊鹏, 张海潇, 曹耿飞, 阿斯哈尔·哈斯木, 纪卫政. 血GP73水平在原发性肝癌TACE疗效评价中的作用[J]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 825-830.

Yifan Li, Diwen Zhu, Weixin Ren, Yingjun Bao, Junpeng Gu, Haixiao Zhang, Gengfei Cao, Weizheng Ji. Role of serum GP73 level in the evaluation of TACE efficacy for primary liver cancer[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(06): 825-830.

目的

分析血高尔基体跨膜糖蛋白73（GP73）在原发性肝癌（肝癌）TACE治疗前后的变化趋势及其与TACE疗效的相关性，探讨血GP73水平在TACE疗效评价中的作用。

方法

本前瞻性研究对象为2020年9月至2021年5月新疆医科大学第一附属医院行TACE治疗的51例肝癌患者。患者均签署知情同意书，符合医学伦理学规定。其中男45例，女6例；年龄42～86岁，中位年龄61岁。选取50例正常人群作为对照。TACE疗效评价采用修改后实体瘤疗效评价标准（mRECIST），根据疗效将患者分为疗效好组（18例）和疗效差组（33例）。ELISA法检测TACE治疗前1 d及术后1、3、5、7、30 d血GP73水平。患者与正常人群血GP73比较采用t检验，GP73表达对TACE疗效的影响分析采用重复测量资料的广义估计方程，相关性分析采用Pearson和Spearman相关性分析。

结果

肝癌患者术前血GP73平均表达量为（0.39±0.25）IU/ml，明显高于正常人群的（0.03±0.01）IU/ml（t=10.841，P＜0.05）。TACE术后1 d的GP73表达量较术前明显升高，术后3、5、7 d连续下降，且疗效好组术后7 d的GP73表达量均值较术前明显降低，而疗效差组术后7 d的GP73表达量与术前表达量相近。疗效好组术后30 d的GP73表达量均值较术前及术后7 d进一步下降，疗效差组术后30 d的GP73表达量较术前及术后7 d明显升高。TACE疗效与时间存在明显交互效应（F=15.037，P＜0.05）。疗效好组与疗效差组术后5、30 d的GP73表达水平差异有统计学意义（t=4.987，26.788；P＜0.05）。术前与术后30 d的GP73变化量与TACE疗效之间存在明显负相关关系（rs=-0.687，P＜0.05）。术前GP73与肿瘤直径存在明显的正相关关系（r=0.543，P＜0.05）。

结论

肝癌TACE治疗前后GP73水平的变化与TACE疗效具有明显负相关性，术后1个月GP73降低水平越大，疗效越好，GP73具有评价TACE疗效的潜在价值。

关键词: 癌，肝细胞, 肝肿瘤, 化学栓塞，治疗性, 高尔基体跨膜糖蛋白（GP73）, 治疗

Objective

To analyze the changing trends of serum Golgi protein 73 （GP73） before and after TACE for primary liver cancer （PLC） and its correlation with efficacy of TACE，aiming to explore the role of serum GP73 level in the evaluation of efficacy of TACE.

Methods

In this prospective study，51 patients with PLC who underwent TACE in the First Affiliated Hospital of Xinjiang Medical University from September 2020 to May 2021 were enrolled. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them，45 patients were male and 6 female，aged 42-86 years，with a median age of 61 years. 50 healthy subjects were selected as normal controls.The efficacy of TACE was evaluated based on the modified response evaluation criteria in solid tumors（mRECIST）. According to efficacy，all patients were divided into the favorable efficacy group （n=18） and poor efficacy group （n=33）. Serum GP73 levels 1 d before TACE and 1，3，5，7 and 30 d after TACE were detected by ELISA. Serum GP73 levels between patients and normal controls were compared by t test.The effect of GP73 expression on TACE efficacy was evaluated by generalized estimation equation of repeated measurement data. Correlation analysis was performed by Pearson's and Spearman's correlation analyses.

Results

The average expression level of GP73 in PLC patients before TACE was （0.39±0.25） IU/ml，significantly higher than （0.03±0.01） IU/ml in normal controls （t=10.841， P＜0.05）. The expression level of GP73 at 1 d after TACE was significantly higher than preoperative level，which was decreased continuously at 3，5 and 7 d after TACE. In the favorable efficacy group，the average expression level of GP73 at postoperative 7 d was significantly lower compared with preoperative level，whereas the expression level of GP73 at postoperative 7 d was similar to that before TACE in the poor efficacy group.In the favorable efficacy group，the average expression level of GP73 at 30 d after TACE was further decreased compared with those before and 7 d after TACE，whereas the expression level of GP73 at 30 d after TACE was significantly higher than those before and 7 d after TACE in the poor efficacy group.There was an evident interaction effect between the efficacy and duration of TACE （F=15.037， P＜0.05）.There was statistical significance in the expression levels of GP73 at postoperative 5 and 30 d between the favorable and poor efficacy groups （t=4.987，26.788； P＜0.05）. A significant negative correlation was found between the changes of GP73 levels before and 30 d after TACE and efficacy of TACE （rs=-0.687， P＜0.05）.An evident positive correlation was found between preoperative GP73 level and tumor diameter （r=0.543，P＜0.05）.

Conclusions

A significant negative correlation is found between the changes of GP73 levels before and after TACE and efficacy of TACE. The greater the decrease of GP73 levels at postoperative 1 month after TACE，the better the efficacy. GP73 level has potential value in evaluating the efficacy of TACE.

Key words: Carcinoma，hepatocellular, Liver neoplasms, Chemoembolization，therapeutic, Golgi protein 73 （GP73）, Treatment outcome
表1 疗效好组与疗效差组肝癌患者一般资料比较
组别 例数 性别（例） 年龄（岁，xˉ±s） Child-Pugh分级（例） 肿瘤大小（cm，xˉ±s） 肿瘤个数（例） 血管侵犯（例）
男 女 A B 1个 ＞1个 有 无
疗效好组 18 16 2 60±9 17 1 5.1±2.3 8 10 1 17
疗效差组 33 29 4 61±11 30 3 8.2±4.1 11 22 4 29
统计值 χ 2=0.011 t=-0.283 χ 2=0.201 t=-2.899 χ 2=0.654 χ 2=0.568
P值 0.915 0.778 0.654 0.006 0.433 0.451
组别 例数 BCLC分期（例） 术式（例） 辅助治疗（例） mRECIST评价（例）
A B C C-TACE D-TACE 化疗 靶向 联合 CR PR SD PD
疗效好组 18 11 6 1 17 1 0 6 0 13 5 0 0
疗效差组 33 12 17 4 26 7 2 10 2 0 0 21 12
统计值 χ 2=2.948 χ 2=2.159 - -
P值 0.229 0.142 0.498 ＜0.001
图1 疗效好组与疗效差组肝癌患者不同时间点GP73表达的变化趋势 注：GP73为高尔基体跨膜糖蛋白
表2 肝癌患者不同TACE疗效及不同时间点GP73表达水平比较（IU/ml，±s）
组别 例数 术前 术后1d 术后3d 术后5d 术后7d 术后30d F值 P值
疗效好组 18 0.47±0.29 0.71±0.31 0.43±0.22 0.34±0.16 0.32±0.16 0.29±0.16 108.880 ＜0.001
疗效差组 33 0.34±0.22 0.64±0.28 0.48±0.27 0.37±0.16 0.31±0.16 0.42±0.23 225.733 ＜0.001
t值 1.901 0.011 -2.807 -4.987 1.265 -26.788
P值 0.063 0.915 0.094 0.026 0.261 ＜0.001
表3 GP73表达水平变化与TACE疗效的相关性分析 ［M（Q1，Q3）］
组别 例数 GP73变化量 GP73变化率
疗效好 18 0.17（0.03，0.36） 0.42（0.15，0.56）
疗效差 33 -0.07（-0.14，-0.03） -0.24（-0.51，0.11）
Z值 -4.455 -4.317
P值 ＜0.001 ＜0.001
图2 术前GP73表达水平与肿瘤直径的关系 注：GP73为高尔基体跨膜糖蛋白
［1］
Sung H，Ferlay J，Siegel RL，et al. Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin，2021，71（3）:209-249.
［2］
Sun L，Fahey P，Zhu X，et al. A cohort study to examine the use of Chinese herbal medicine in combination with conventional therapies for patients with hepatocellular carcinoma in China［J］. Integr Cancer Ther，2018，17（3）:902-911.
［3］
Park JW，Chen M，Colombo M，et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study［J］. Liver Int，2015，35（9）:2155-2166.
［4］
Lencioni R，de Baere T，Soulen MC，et al. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: a systematic review of efficacy and safety data［J］. Hepatology，2016，64（1）:106-116.
［5］
Bruix J，Sherman M，American Association for the Study of Liver Diseases. management of hepatocellular carcinoma: an update［J］.Hepatology，2011，53（3）:1020-1022.
［6］
Nagasue N，Galizia G，Kohno H，et al. Adverse effects of preoperative hepatic artery chemoembolization for resectable hepatocellular carcinoma: a retrospective comparison of 138 liver resections［J］. Surgery，1989，106（1）:81-86.
［7］
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma［J］.J Hepatol，2018，69（1）:182-236.
［8］
Kokudo N，Takemura N，Hasegawa K，et al. Clinical practice guidelines for hepatocellular carcinoma: the Japan Society of Hepatology 2017 （4th JSH-HCC guidelines） 2019 update［J］. Hepatol Res，2019，49（10）:1109-1113.
［9］
中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范（2019年版）［J］. 临床肝胆病杂志，2020，36（2）:277-292.
［10］
Wang Y，Wan YJY. Golgi protein 73，hepatocellular carcinoma and other types of cancers［J］. Liver Res，2020，4（4）:161-167.
［11］
Kladney RD，Bulla GA，Guo L，et al. GP73，a novel Golgi-localized protein upregulated by viral infection［J］. Gene，2000，249（1/2）:53-65.
［12］
Bao YX，Cao Q，Yang Y，et al. Expression and prognostic significance of golgiglycoprotein73 （GP73） with epithelialmesenchymal transition （EMT） related molecules in hepatocellular carcinoma （HCC）［J］. Diagn Pathol，2013，8:197.
［13］
Yang Y，Liu Q，Li Z，et al. GP73 promotes epithelial-mesenchymal transition and invasion partly by activating TGF-β1/Smad2 signaling in hepatocellular carcinoma［J］. Carcinogenesis，2018，39（7）:900-910.
［14］
余晨曦，滕皋军. 经导管动脉化疗栓塞术抵抗研究进展［J］. 介入放射学杂志，2017，26（12）:1063-1067.
［15］
Raoul JL，Gilabert M，Piana G. How to define transarterial chemoembolization failure or refractoriness: a European perspective［J］. Liver Cancer，2014，3（2）:119-124.
［16］
Kim HY，Park JW，Joo J，et al. Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma［J］. J Gastroenterol Hepatol，2012，27（6）:1051-1056.
［17］
Kudo M，Matsui O，Izumi N，et al. Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update［J］. Oncology，2014，87（Suppl 1）:22-31.
［18］
Mao Y，Yang H，Xu H，et al. Golgi protein 73 （GOLPH2） is a valuable serum marker for hepatocellular carcinoma［J］. Gut，2010，59（12）:1687-1693.
［19］
Yang Y，Liu Q，Zhang H，et al. Silencing of GP73 inhibits invasion and metastasis via suppression of epithelial-mesenchymal transition in hepatocellular carcinoma［J］. Oncol Rep，2017，37（2）:1182-1188.
［20］
Ai N，Liu W，Li ZG，et al. High expression of GP73 in primary hepatocellular carcinoma and its function in the assessment of transcatheter arterial chemoembolization［J］. Oncol Lett，2017，14（4）:3953-3958.
［21］
Pan J，Zhang YF，Yang HY，et al. The response of Golgi protein 73 to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma may relate to the influence of certain chemotherapeutics［J］. Hepatobiliary Pancreat Dis Int，2015，14（4）:406-412.
[1] 史学兵, 谢迎东, 谢霓, 徐超丽, 杨斌, 孙帼. 声辐射力弹性成像对不可切除肝细胞癌门静脉癌栓患者放射治疗效果的评价[J]. 中华医学超声杂志（电子版）, 2024, 21(08): 778-784.
[2] 赖全友, 高远, 汪建林, 屈士斌, 魏丹, 彭伟. 三维重建技术结合腹腔镜精准肝切除术对肝癌患者术后CD4+、CD8+及免疫球蛋白水平的影响[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 651-654.
[3] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[4] 许月芳, 刘旺, 曾妙甜, 郭宇姝. 多粘菌素B和多粘菌素E治疗外科多重耐药菌感染临床疗效及安全性分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 700-703.
[5] 梁孟杰, 朱欢欢, 王行舟, 江航, 艾世超, 孙锋, 宋鹏, 王萌, 刘颂, 夏雪峰, 杜峻峰, 傅双, 陆晓峰, 沈晓菲, 管文贤. 联合免疫治疗的胃癌转化治疗患者预后及术后并发症分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 619-623.
[6] 王秋生. 胆道良性疾病诊疗策略[J]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 779-782.
[7] 公宇, 廖媛, 尚梅. 肝细胞癌TACE术后复发影响因素及预测模型建立[J]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 818-824.
[8] 中华医学会器官移植学分会. 肝移植术后缺血性胆道病变诊断与治疗中国实践指南[J]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 739-748.
[9] 陈伟杰, 何小东. 胆囊癌免疫靶向治疗进展[J]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 763-768.
[10] 翁桂湖, 刘悦泽, 张太平. 胰腺神经内分泌肿瘤治疗进展与争议[J]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 602-606.
[11] 王妍, 李征, 卓奇峰, 周陈杰, 吉顺荣, 徐晓武, 陈洁, 虞先濬. 微小无功能性胰腺神经内分泌瘤外科治疗进展[J]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 607-614.
[12] 崔军威, 蔡华丽, 胡艺冰, 胡慧. 亚甲蓝联合金属定位夹及定位钩针标记在乳腺癌辅助化疗后评估腋窝转移淋巴结的临床应用价值探究[J]. 中华临床医师杂志(电子版), 2024, 18(07): 625-632.
[13] 王誉英, 刘世伟, 王睿, 曾娅玲, 涂禧慧, 张蒲蓉. 老年乳腺癌新辅助治疗病理完全缓解的预测因素分析[J]. 中华临床医师杂志(电子版), 2024, 18(07): 641-646.
[14] 张平骥, 徐钰, 李天水, 庞文翼, 符师宁, 张梦圆. 重症患者镇静治疗现状及期望的调查研究[J]. 中华临床医师杂志(电子版), 2024, 18(06): 562-567.
[15] 王昌前, 林婷婷, 宁雨露, 王颖杰, 谭文勇. 光免疫治疗在肿瘤领域的临床应用新进展[J]. 中华临床医师杂志(电子版), 2024, 18(06): 575-583.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号