目的: 探讨血清甲胎蛋白(alpha-fetoprotein,AFP)、趋化因子配体10(chemokine ligand 10,CXCL10)-mRNA、巯基氧化酶1(quiescin sulfhydryl oxidase 1,QSOX1)-mRNA的检测在乙肝病毒相关肝细胞肝癌(hepatocellular carcinoma,HCC)诊断中的临床应用价值。方法: 选取2022年1月—2023年5月长沙市第一医院感染科住院患者及体检中心健康人群共120例为研究对象,其中包括50例乙肝相关早期HCC患者(肝细胞癌组)、40例肝硬化组以及30例正常对照组;采用RT-PCR方法检测外周血CXCL10-mRNA、QSOX1-mRNA表达,放射免疫法检测AFP水平;比较3 组血清CXCL10-mRNA、QSOX1-mRNA、AFP水平差异,并绘制受试者工作曲线,分析CXCL10-mRNA、QSOX1-mRNA、AFP 指标检测在HBV相关HCC早期诊断效能。结果: 肝细胞癌组患者外周血中检测到AFP的阳性率高于肝硬化组,差异有统计学意义;肝细胞癌组患者CXCL10-mRNA、QSOX1-mRNA、AFP表达水平均高于肝硬化组及健康对照组;肝硬化组血清CXCL10-mRNA、QSOX1-mRNA水平显著高于对照组;采用ROC曲线分析显示,CXCL10-mRNA、QSOX1-mRNA、AFP指标检测诊断早期HBV-HCC的AUC 分别为0.881,0.790、0.814;三个指标联合检测AUC为0.957,诊断HCC的敏感度和特异度分别达到0.860和0.971,高于3种标志物单独检测的敏感度和特异度,诊断效能高于单一检测。结论: CXCL10-mRNA、QSOX1-mRNA水平在HBV相关HCC及肝硬化患者血清中呈高表达,两者与AFP联合检测能够提升乙肝相关性HCC的早期诊断效率。
Abstract
Objective To explore the clinical application value of serum alpha-fetoprotein (AFP), CXCL10-mRNA, and QSOX1-mRNA detection in the diagnosis of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). Methods A total of 120 subjects were selected from hospitalized patients in the Department of Infectious Diseases and healthy individuals from the physical examination center at The First Hospital of Changsha from January 2022 to May 2023. The subjects included 50 patients with early HBV-related HCC, 40 patients with liver cirrhosis, and 30 healthy individuals. The expression levels of peripheral blood CXCL10-mRNA and QSOX1-mRNA were detected by RT-PCR, and the AFP level was measured using a radioimmunoassay. The differences in serum levels of CXCL10-mRNA, QSOX1-mRNA, and AFP among the three groups were compared. Receiver operating characteristic (ROC) curves were plotted, and the diagnostic value of CXCL10-mRNA, QSOX1-mRNA, and AFP markers in the early diagnosis of HBV-related HCC was analyzed. Results The positive rate of AFP detection in the peripheral blood of the hepatocellular carcinoma (HCC) group patients was higher than that in the liver cirrhosis group, and the difference was statistically significant (P<0.05). The expression levels of CXCL10-mRNA, QSOX1-mRNA, and AFP in the HCC group were higher than those in the liver cirrhosis group and the healthy control group (P<0.05). The serum levels of CXCL10-mRNA and QSOX1-mRNA in the liver cirrhosis group were significantly higher than those in the healthy control group (P<0.05). ROC curve analysis showed that the area under the curve (AUC) for CXCL10-mRNA, QSOX1-mRNA, and AFP in the early diagnosis of HBV-related HCC was 0.881, 0.790, and 0.814 respectively. The AUC for the combined detection of the three markers was 0.957, with a sensitivity and specificity for diagnosing HCC of 0.860 and 0.971, respectively, which were higher than those for the individual markers, indicating higher diagnostic performance. Conclusion The levels of CXCL10-mRNA and QSOX1-mRNA are highly expressed in the serum of patients with HBV-related HCC and cirrhosis. Combined detection of these markers with AFP can improve the early diagnostic efficiency of HBV-related HCC.
关键词
趋化因子配体10 /
巯基氧化酶1 /
甲胎蛋白 /
HBV相关肝细胞癌
Key words
chemokine ligand 10 /
quiescin sulfhydryl oxidase 1 /
alpha-fetoprotein /
hepatitis B virus-related hepatocellular carcinoma
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] BRAY F,LAVERSANNE M,SUNG H,et al.Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2024,74(3):229-263.
[2] 李曾, 谢青, 李金强. QSOX1、CXCL10、β2GPI在乙型肝炎病毒相关性肝病患者中的表达及相关性研究[J]. 中国感染与化疗杂志, 2021, 21(05): 588-592.
[3] 张婧, 陈洁, 关贵文, 等. 肝细胞癌中趋化因子CXCL10及其受体CXCR3的表达及临床意义分析[J]. 北京大学学报 (医学版), 2019, 51(03): 402-408.
[4] 陈星, 戢敏, 喻雪琴, 等. 循环血CCL2、CCL5、CXCL10在HBV相关性肝病中表达水平的差异及相关性分析[J]. 川北医学院学报, 2019, 34(03): 354-358.
[5] 冯学敏, 郑文琪. 静息巯基氧化酶1在肿瘤微环境中的作用研究进展[J]. 生命的化学, 2020, 40(09): 1571-1575.
[6] TAL F, IRIS G, YOAV E, et al.Inhibition of fibroblast secreted QSOX1 perturbs extracellular matrix in the tumor microenvironment and decreases tumor growth and metastasis in murine cancer models[J]. Oncotarget, 2020, 11(4): 386-398.
[7] 国家卫生健康委. 原发性肝癌诊疗指南 (2022年版)[J]. 肿瘤综合治疗电子杂志, 2022, 8(02): 16-53.
[8] 林勇, 曾欣, 胡平方. 中国肝硬化临床诊治共识意见[J]. 临床肝胆病杂志, 2023, 39(09): 2057-2073.
[9] 尤红, 王福生, 李太生, 等. 慢性乙型肝炎防治指南 (2022年版)[J]. 实用肝脏病杂志, 2023, 26(03): 457-478.
[10] HAN B,ZHENG R,ZENG H,et al.Cancer incidence and mortality in China,2022[J]. Journal of the National Cancer Center,2024,4(1):47-53.
[11] DHANASEKARAN R, BANDOH S, ROBERTS LR. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances[J]. F1000 Research, 2016, 5: F1000 Faculty Rev-879.
[12] 南月敏, 高沿航, 王荣琦, 等. 原发性肝癌二级预防共识 (2021年版)[J]. 临床肝胆病杂志, 2021, 37(03): 532-542.
[13] 邓文俊, 胡连涛, 赵彬男, 等. CXC趋化因子配体10对肝细胞癌SMMC-7721细胞增殖和迁移的影响及其机制[J]. 吉林大学学报 (医学版), 2023, 49(05): 1227-1233.
[14] JAVITT G, GROSSMAN-HAHAM I, ALON A, et al.cis-Proline mutants of quiescin sulfhydryl oxidase 1 with altered redox properties undermine extracellular matrix integrity and cell adhesion in fibroblast cultures[J]. Protein Sci, 2019, 28(1): 228-238.
[15] FIFIELD AL, HANAVAN PD, FAIGEL DO, et al.Molecular Inhibitor of QSOX1 Suppresses Tumor Growth In Vivo[J]. Molecular cancer therapeutics, 2020, 19(1): 112-122.
[16] 钟嘉宁. 巯基氧化酶1与HBV相关性肝病的相关性研究及其在肝癌生长中的作用初探[D]. 南宁: 广西医科大学, 2019.
[17] JIALEI S, CHENHAO Z, YUE Z, et al.Quiescin sulfhydryl oxidase 1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by driving EGFR endosomal trafficking and inhibiting NRF2 activation[J]. Redox Biology, 2021, 41101942-101942.
[18] 应慧文, 曹桂莲, 张弦. USP7和DNMT1在乙肝相关性肝癌中的表达及意义[J]. 南通大学学报 (医学版), 2023, 43(06): 531-535.
[19] 傅丽敏, 徐冬梅, 朱艳. AFP、PIVKA-Ⅱ和NLR在HBV-HCC中的诊断价值探讨[J]. 浙江临床医学, 2023, 25(10): 1532-1534.
基金
2022年湖南省卫生健康委科研计划项目“血清CXCL10、QSOX1联合AFP对HBV相关肝细胞癌早期诊断的临床研究”(202203082996)