PDF下载 ( 2613 KB)
Value of serum autophagy-related protein 7 in diagnosis of HBV-related hepatocellular carcinoma
-
摘要:
目的 通过分析HBV相关肝细胞癌(HBV-HCC)患者血清自噬相关蛋白7(ATG7)的表达水平，探讨其在HBV-HCC诊断中的临床意义。 方法 选取2018年6月—2020年12月在福建医科大学孟超肝胆医院住院的慢性乙型肝炎(CHB)患者50例，HCC患者89例，其中HBV-HCC患者67例，非HBV-HCC(nonHBV-HCC)患者22例，另选取同期20例健康体检者为对照(HC)。采集各组个体人口学及AFP等实验室数据，应用ELISA技术检测各组样本血清ATG7水平，绘制ATG7、AFP及二者联合检测受试者工作特征曲线(ROC曲线)并比较其曲线下面积(AUC)。非正态分布的计量资料多组间比较采用Kruskal-Wallis H检验，2组间比较采用Mann-Whitney U检验；计数资料组间比较采用χ2检验；采用Spearman进行相关性分析。 结果 HBV-HCC组、nonHBV-HCC组、CHB组和HC组的血清ATG7水平分别为22.88(19.79~23.04) ng/mL、17.06(14.45~19.40)ng/mL、19.21(16.65~20.82)ng/mL和13.82(8.70~17.82)ng/mL，差异有统计学意义(χ2=65.144，P＜0.001)；ATG7诊断HBV-HCC的AUC为0.818(95%CI：0.743~0.879)，略高于AFP(AUC=0.777，95%CI：0.698~0.843)，差异无统计学意义(Z=0.852，P=0.394)；ATG7和AFP联合检测诊断HBV-HCC的AUC为0.859(95%CI：0.790~0.913)，显著高于ATG7(Z=2.192，P=0.028)和AFP(Z=2.076，P=0.038)。 结论 ATG7是诊断HBV-HCC的良好标志物，ATG7和AFP联合检测可显著提高HBV-HCC的诊断率。 Abstract:Objective To investigate the clinical significance of autophagy-related protein 7 (ATG7) in the diagnosis of HBV-related hepatocellular carcinoma (HBV-HCC) by measuring the expression level of serum ATG7 in patients with HBV-HCC. Methods A total of 50 patients with chronic hepatitis B (CHB) and 89 patients with HCC who were hospitalized in Mengchao Hepatobiliary Hospital of Fujian Medical University from June 2018 to December 2020 were enrolled, among whom 67 patients had HBV-HCC (HBV-HCC group) and 22 patients had no HBV-HCC (non-HBV-HCC group), and 20 healthy volunteers who underwent physical examination were enrolled as healthy control (HC) group. Demographic data and laboratory data including alpha-fetoprotein (AFP) were collected from each group, and ELISA was used to measure the serum level of ATG7. The receiver operating curve (ROC) was plotted for ATG7 and AFP used alone or in combination, and the area under the ROC curve (AUC) was compared. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups; a Spearman correlation analysis was used to investigate correlation. Results The serum level of ATG7 was 22.88(19.79-23.04) ng/mL in the HBV-HCC group, 17.06(14.45-19.40) ng/mL in the non-HBV-HCC group, 19.21(16.65-20.82) ng/mL in the CHB group, and 13.82(8.70-17.82) ng/mL in the HC group, with a significant difference between groups (χ2=65.144, P < 0.001). ATG7 had an AUC of 0.818 (95% confidence interval [CI]: 0.743-0.879) and AFP had an AUC of 0.777 (95% CI: 0.698-0.843) in the diagnosis of HBV-HCC, suggesting that ATG7 had a slightly higher AUC than AFP (Z=0.852, P=0.394). ATG7 combined with AFP had an AUC of 0.859 (95% CI: 0.790-0.913) in the diagnosis of HBV-HCC, which was significantly higher than the AUC of ATG7 alone (Z=2.192, P=0.028) and AFP alone (Z=2.076, P=0.038). Conclusion ATG7 is a good marker for the diagnosis of HBV-HCC, and combined measurement of ATG7 and AFP can significantly improve the diagnostic rate for HBV-HCC. -
表 1 3组人口学和实验室特征比较
参数 HCC组(n=89) CHB组(n=50) HC组(n=20) χ2值 P值 年龄(岁) 56.0(48.0~66.5) 42.0(32.8~52.5) 37.5(30.0~48.8) 38.807 ＜0.001 男性[例(%)] 77(86.52) 38(76.00) 13(65.00) 5.480 0.076 TBil(μmol/L) 19.30(12.65~26.10) 19.55(12.78~29.28) 12.15(9.48~18.63) 10.478 0.005 DBil(μmol/L) 7.60(4.70~10.85) 4.45(2.20~7.05) 5.30(4.15~6.35) 17.168 ＜0.001 TP(g/L) 61.0(54.5~67.5) 66.5(60.8~73.3) 72.0(70.0~77.0) 34.168 ＜0.001 Alb(g/L) 34.0(31.0~38.5) 37.5(34.0~41.0) 44.0(41.0~47.0) 42.516 ＜0.001 ALT(U/L) 115.0(62.0~218.5) 87.5(26.5~206.8) 19.0(12.3~26.5) 37.212 ＜0.001 AST(U/L) 149.0(54.0~286.0) 57.0(31.5~110.5) 17.0(14.3~20.0) 54.345 ＜0.001 GGT(U/L) 52.0(34.0~110.5) 68.5(29.3~112.0) 17.0(14.3~24.5) 31.527 ＜0.001 ALP(U/L) 81.0(60.5~103.0) 102.0(82.5~117.0) 66.5(52.8~88.3) 21.160 ＜0.001 AFP(ng/mL) 37.90(5.00~712.32) 7.20(3.05~241.27) 2.85(2.18~4.48) 33.048 ＜0.001 ATG7(ng/mL) 21.11(17.76~22.73) 19.21(16.65~20.82) 13.82(8.70~17.82) 33.134 ＜0.001 
下载: 导出CSV
表 2 HBV-HCC组与nonHBV-HCC组生化和病理特征比较
参数 HBV-HCC组(n=67) nonHBV-HCC组(n=22) 统计值 P值 年龄(岁) 55.0(46.0~ 65.0) 63.5(50.8~71.8) U=535.000 0.055 男/女(例) 58/9 19/3 χ2=0.001 0.981 TBil(μmol/L) 20.60(13.30~27.40) 16.00(11.15~21.48) U=524.500 0.043 DBil(μmol/L) 7.70(4.80~10.90) 7.15(3.80~9.65) U=602.500 0.201 TP(g/L) 61.0(50.0~67.0) 58.5(51.3~68.3) U=638.500 0.348 Alb(g/L) 34.0(31.0~38.0) 33.0(30.3~39.0) U=709.500 0.793 ALT(U/L) 95.0(54.0~198.0) 152.0(89.8~268.0) U=557.000 0.087 AST(U/L) 136.0(37.0~240.0) 236.5(93.8~348.8) U=523.000 0.042 GGT(U/L) 51.0(30.0~111.0) 58.0(35.0~113.3) U=658.000 0.452 ALP(U/L) 76.0(60.0~99.0) 92.0(62.8~127.8) U=575.500 0.124 AFP(ng/mL) 58.00(7.10~945.80) 18.28(2.48~405.33) U=536.500 0.057 BCLC(A/B/C/D，例) 51/4/12/0 12/5/5/0 χ2=5.229 0.073 最大肿瘤直径(cm) 3.95(2.50~7.70) 8.00(3.70~11.00) U=520.000 0.047 肝硬化[例(%)] 55(82.09) 9(40.91) χ2=13.904 ＜0.001
下载: 导出CSV
表 3 ATG7、AFP及其联合检测诊断HBV-HCC的性能
项目 AUC cut-off值 敏感度(%) 特异度(%) 阳性预测值(%) 阴性预测值(%) AFP 0.777 12.20 ng/mL 68.66 74.29 71.9 71.2 ATG7 0.818 20.08 ng/mL 71.64 77.14 75.0 74.0 ATG7+AFP 0.859 0.56 74.63 88.57 86.2 78.5
下载: 导出CSV
-
[1] ZHENG RS, SUN KX, ZHANG SW, et al. Report of cancer epidemiology in China, 2015[J]. Chin J Oncol, 2019, 41(1): 19-28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.005.郑荣寿, 孙可欣, 张四维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.005. [2] WANG M, WANG Y, FENG X, et al. Contribution of hepatitis B virus and hepatitis C virus to liver cancer in China north areas: Experience of the Chinese National Cancer Center[J]. Int J Infect Dis, 2017, 65: 15-21. DOI: 10.1016/j.ijid.2017.09.003. [3] SHIN GC, KANG HS, LEE AR, et al. Hepatitis B virus-triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response[J]. Autophagy, 2016, 12(12): 2451-2466. DOI: 10.1080/15548627.2016.1239002. [4] TIAN Y, SIR D, KUO CF, et al. Autophagy required for hepatitis B virus replication in transgenic mice[J]. J Virol, 2011, 85(24): 13453-13456. DOI: 10.1128/JVI.06064-11. [5] AKKOÇ Y, GÖZVAÇ1K D. Autophagy and liver cancer[J]. Turk J Gastroenterol, 2018, 29(3): 270-282. DOI: 10.5152/tjg.2018.150318. [6] XIE M, YANG Z, LIU Y, et al. The role of HBV-induced autophagy in HBV replication and HBV related-HCC[J]. Life Sci, 2018, 205: 107-112. DOI: 10.1016/j.lfs.2018.04.051. [7] WANG YL, XU XY, YU XH, et al. Role of oxidative stress and autophagy in the development an progression of hepatocellular carcinoma[J]. J Clin Hepatol, 2020, 36(2): 426-429. DOI: 10.3969/j.issn.1001-5256.2020.02.042.王雨露, 许笑阳, 俞晓菡, 等. 氧化应激与自噬在肝细胞癌发生发展中的作用[J]. 临床肝胆病杂志, 2020, 36(2): 426-429. DOI: 10.3969/j.issn.1001-5256.2020.02.042. [8] National Health and Family Planning Commission of the People's Republic of China. Diagnosis, management, and treatment of hepatocellular carcinoma (V2017)[J]. J Clin Hepatol, 2017, 33(8): 1419-1431. DOI: 10.3969/j.issn.1001-5256.2017.08.003.中华人民共和国国家卫生和计划生育委员会. 原发性肝癌诊疗规范(2017版)[J]. 临床肝胆病杂志, 2017, 33(8): 1419-1431. DOI: 10.3969/j.issn.1001-5256.2017.08.003. [9] Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. [10] MIZUSHIMA N, YOSHIMORI T, OHSUMI Y. The role of Atg proteins in autophagosome formation[J]. Annu Rev Cell Dev Biol, 2011, 27: 107-132. DOI: 10.1146/annurev-cellbio-092910-154005. [11] SIR D, TIAN Y, CHEN WL, et al. The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication[J]. Proc Natl Acad Sci U S A, 2010, 107(9): 4383-4388. DOI: 10.1073/pnas.0911373107. [12] WANG Y, CHE Y, GAO YX, et al. Effect of expression of autophagy related gene Atg7 on replication of hepatitis B virus[J]. China Medical Herald, 2020, 17(2): 4-8. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202002002.htm王阳, 车阳, 高玉雪, 等. 自噬相关蛋白基因Atg7的表达对乙型肝炎病毒复制的影响[J]. 中国医药导报, 2020, 17(2): 4-8. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202002002.htm [13] OU Y, HE J, LIU Y. MiR-490-3p inhibits autophagy via targeting ATG7 in hepatocellular carcinoma[J]. IUBMB Life, 2018, 70(6): 468-478. DOI: 10.1002/iub.1715. [14] YU H, LIU QH, XIAO PL, et al. Expression and clinical significance of Beclin1, LC3 and mTOR in hepatic carcinioma[J]. Anhui Med Pharmaceut J, 2018, 22(2): 246-249. DOI: 10.3969/j.issn.1009-6469.2018.02.014.于海, 刘清华, 肖培伦, 等. Beclin1、LC3和mTOR在肝癌中的表达及临床意义[J]. 安徽医药, 2018, 22(2): 246-249. DOI: 10.3969/j.issn.1009-6469.2018.02.014. [15] YANG L, ZHANG X, LI H, et al. The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma[J]. Mol Biosyst, 2016, 12(8): 2605-2612. DOI: 10.1039/c6mb00114a. [16] LUO T, FU J, XU A, et al. PSMD10/gankyrin induces autophagy to promote tumor progression through cytoplasmic interaction with ATG7 and nuclear transactivation of ATG7 expression[J]. Autophagy, 2016, 12(8): 1355-1371. DOI: 10.1080/15548627.2015.1034405. [17] NITURE S, GYAMFI MA, LIN M, et al. TNFAIP8 regulates autophagy, cell steatosis, and promotes hepatocellular carcinoma cell proliferation[J]. Cell Death Dis, 2020, 113(3): 178. DOI: 1038/s41419-020-2369-4. [18] SUN T, TANG Y, SUN D, et al. Osteopontin versus alpha-fetoprotein as a diagnostic marker for hepatocellular carcinoma: A meta-analysis[J]. Onco Targets Ther, 2018, 11: 8925-8935. DOI: 10.2147/OTT.S186230. [19] QUN ZJ, SHEN Y, CUI XL, et al. Application of logistic regression in multi-index combined diagnosis of diseases[J]. Chin J Health Statistics, 2014, 31(1): 116-118. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWT201401036.htm秦正积, 沈毅, 崔晓莉, 等. logistic回归在疾病多指标联合诊断中的应用[J]. 中国卫生统计, 2014, 31(1): 116-118. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWT201401036.htm -
本文二维码
图(3) / 表(3)
计量
- 文章访问数: 572
- HTML全文浏览量: 104
- PDF下载量: 42
- 被引次数: 0
