[1]王 娟,杨 柳,刘家云.肝癌患者血浆ctDNA SCNM1甲基化水平检测及与临床预后评估价值研究[J].现代检验医学杂志,2024,39(06):18-22+36.[doi:10.3969/j.issn.1671-7414.2024.06.003]
　WANG Juan,YANG Liu,LIU Jiayun.Plasma ctDNA SCNM1 Methylation Level and Its Clinical Prognostic Value in Hepatocellular Carcinoma Patients[J].Journal of Modern Laboratory Medicine,2024,39(06):18-22+36.[doi:10.3969/j.issn.1671-7414.2024.06.003]
点击复制

肝癌患者血浆ctDNA SCNM1甲基化水平检测及与临床预后评估价值研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年06期
页码:
18-22+36
栏目:
论著
出版日期:
2024-11-15

文章信息/Info

Title:
Plasma ctDNA SCNM1 Methylation Level and Its Clinical Prognostic Value in Hepatocellular Carcinoma Patients
文章编号:
1671-7414（2024）06-018-06
作者:
王 娟; 杨 柳; 刘家云
（空军军医大学第一附属医院检验科，西安 710032）
Author(s):
WANG Juan;  YANG Liu;  LIU Jiayun
（Department of Clinical Laboratory，the First Affiliated Hospital，Air Force Medical University(AFMU), Xi’an 710032，China）
关键词:
循环肿瘤DNA; 钠离子通道调节蛋白1; 肝细胞癌; 甲基化
分类号:
R735.7；R730.43
DOI:
10.3969/j.issn.1671-7414.2024.06.003
文献标志码:
A
摘要:
目的 探讨肝细胞癌（hepatocellular carcinoma，HCC）患者血浆游离肿瘤DNA (circulating tumour DNA，ctDNA) 中钠离子通道调节蛋白1(sodium channel modifier 1，SCNM1) 甲基化水平与患者预后的关系。方法 选择2018年6 月～ 2020 年12 月空军军医大学第一附属医院收治的67 例肝细胞癌患者作为HCC 组，同期健康人群50 例作为对照组，收集对比患者临床资料。微滴式数字PCR（droplet digital PCR，ddPCR）检测血浆ctDNA SCNM1 甲基化水平。比较不同组别间血清甲胎蛋白（alpha fetoprotein，AFP）、丙氨酸氨基转移酶（cereal third transaminase，ALT）、天冬氨酸氨基转移酶（aspartate transaminase，AST）、ctDNA 水平和SCNM1 甲基化比率的差异；比较不同SCNM1 甲基化水平和不同预后患者临床病理特征差异，多因素COX 回归分析肝细胞癌患者的预后影响因素；受试者工作特征（ROC）曲线分析SCNM1 甲基化水平对预后判断的灵敏度和特异度。结果 HCC 组血浆AFP 水平[351.00（14.90，1 210.00）ng/ml]、ctDNA 水平[57.65（15.79，171.90）ng/ml]、SCNM1 甲基化水平[13.23%（4.36%，26.61%）] 均高于对照组［2.90（2.20，5.10）ng/ml，15.75（12.85，21.07）ng/ml，4.69%（3.30%，6.68%）］，差异具有统计学意义（Z=-7.18，-5.00，-4.77，均P < 0.05）；肿瘤病灶直径＞ 2cm，HCC 远处转移患者的SCNM1 甲基化呈现高水平（χ2=5.01，38.85，均P < 0.05）；SCNM1 甲基化检测高水平组患者中位生存期短于低水平组（13.31 月vs. 24.44 月），差异具有统计学意义（Log rankχ2 = 4.141，P = 0.04），SCNM1 甲基化高水平是患者生存的独立影响因素（95% CI：2.449 ～ 62.716，P = 0.002）；SCNM1 甲基化预测肝细胞癌患者病情进展的AUC（95% CI）为0.716（0.583 ～ 0.848），其敏感度和特异度分别为63.0% 和81.1%。SCNM1 甲基化、ctDNA 联合AFP 对肝细胞癌进展预测的AUC（95%CI）为0.747（0.618 ～ 0.875），敏感度和特异度分别为55.6%，91.9%。结论 SCNM1 甲基化高水平提示HCC 患者预后不良，是患者生存的独立影响因素，SCNM1 甲基化、ctDNA，联合AFP 检测可作为预后判断标志物。
Abstract:
Objective To investigate the relationship between prognostic value and methylated expression level of circulating tumour DNA (ctDNA) sodium channel modifier 1 (SCNM1) in plasma of patients with hepatocellular carcinoma（HCC）. Methods A total of 67 patients with confirmed HCC admitted to the First Affiliated Hospital of AFMU from June 2018 to December 2020 were selected as the research objects. At the same time, 50 healthy volunteers were selected as the control group. Their clinical and pathological data were collected and compared. The methylation level of SCNM1 was detected by droplet digital PCR (ddPCR). The differences of alpha fetoprotein (AFP)，cereal third transaminase(ALT)，aspartate transaminase (AST)， ctDNA，SCNM1 between HCC group and control group were analyzed. Multivariate COX regression risk model was performed to analyze the risk factors of HCC patients. Receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of SCNM1 methylation levels methylation levels. Results AFP [351.00（14.90, 1 210.00）ng/ml]，ctDNA[57.65 （15.79，171.90）ng/ml] and the methylated SCNM1 levels [13.23%（4.36%，26.61%）] in plasma in HCC group were higher than those in control group［2.90（2.20，5.10）ng/ml，15.75（12.85，21.07）ng/ml，4.69%（3.30%，6.68%）］, and the differences were statistically significant (Z=-7.18，-5.00，-4.77，all P < 0.05). High level of SCNM1 methylation was found in HCC patients with tumor lesion diameter > 2cm and distant metastasis（χ2=5.01，38.85，all P < 0.05). The median survival was shorter in the high-methlated SCNM1 group than that in the low-methylated SCNM1 group (13.31 month vs 24.44 month) with significant difference (Log rankχ2 = 4.141, P = 0.04). High SCNM1 methylation level was independent risk factor for HCC patients survival (95% CI: 2.449 ～ 62.716，P=0.002). The ROC curve showed prognostic value of increased methylated SCNM1 was 0.716 (95% CI: 0.583 ～ 0.848), and the sensitivity and specificity were 63.0% and 81.1%, respectively. When combined with plasma SCNM1 methylation level, ctDNA and AFP, the AUC（95% CI） of HCC progression was 0.747 （0.618 ～ 0.875), and the sensitivity and specificity were 55.6% and 91.9%, respectively, which has potential application value for dynamic monitoring of liver cancer patients. Conclusion The high level of methylated SCNM1 in plasma indicates the HCC poor prognosis, and serves as an independent determinant of patient survival. Methylated SCNM1, ctDNA combined with AFP detection can serve as prognostic markers.

参考文献/References:

[1] SINGH D, VIGNAT J, LORENZONI V, et al. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative[J]. Lancet Global Health, 2023, 11(2): e197-e206.
[2] 卢美红, 杨曙梅, 王峰, 等. 血清miRNA-574-3p,AFP,IGF-2 水平联合检测在肝癌早期诊断中的价值研究[J]. 现代检验医学杂志, 2022, 37(2): 33-36. LU Meihong, YANG Shumei, WANG Feng, et al. Study on the value of combined detection of serum miRNA-574-3p, AFP and IGF-2 levels in the early diagnosis of liver cancer[J].Journal of Modern Laboratory Medicine,2022, 37(2): 33-36.
[3] 刘国振, 陈秀余, 张修欢. 血清miR-122-5p,miR-486-5p,AFP 及AFP-L3 水平联合检测对原发性肝癌的诊断价值[J]. 现代检验医学杂志, 2022, 37(1):82-87. LIU Guozhen, CHEN Xiuyu, ZHANG Xiuhuan. Value of combined detection of serum miR-122-5p, miR-486-5p, AFP and AFP-L3 levels in the diagnosis of primary liver cancer[J]. Journal of Modern Laboratory Medicine, 2022, 37(1): 82-87.
[4] NISHIYAMA A, NAKANISHI M. Navigating the DNA methylation landscape of cancer[J]. Trends in Genetics,2021, 37(11): 1012-1027.
[5] NEWHOOK T E, OVERMAN M J, CHUN Y S, et al. Prospective study of perioperative circulating tumor DNA dynamics in patients undergoing hepatectomy for colorectal liver metastases[J]. Annals of Surgery, 2023,277(5): 813-820.
[6] ROY D, TIIRIKAINEN M. Diagnostic power of DNA methylation classifiers for early detection of cancer[J]. Trends in Cancer, 2020, 6(2): 78-81.
[7] WANG Xiangyu, ZHANG Rui, HAN Jiahao, et al. Early circulating tumor DNA dynamics predict neoadjuvant therapy response and recurrence in colorectal liver metastases: a prospective study[J]. Annals of Surgical Oncology, 2023, 30(8): 5252-5263.
[8] WANG Juan, YANG Liu, DIAO Yanjun, et al. Circulating tumour DNA methylation in hepatocellular carcinoma diagnosis using digital droplet PCR[J]. the Journal of International Medical Research, 2021, 49(3): 300060521992962.
[9] HUANG Chenjun, XIAO Xiao, TONG Lin, et al. Risks and clinical predictors of hepatocellular carcinoma in Chinese populations: a real-world study of 10 359 patients in six medical centers [J]. Journal of hepatocellular Carcinoma, 2024, 11: 411-425.
[10] ZHOU Maigeng, WANG Haidong, ZENG Xinying, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017:a systematic analysis for the Global Burden of Disease Study 2017[J].Lancet (London,England),2019,394(10204):1145-1158.
[11] LUO Huiyan, WEI Wei, YE Ziyi, et al. Liquid biopsy of methylation biomarkers in cell-free DNA[J]. Trends in Molecular Medicine, 2021, 27(5): 482-500.
[12] YE Qianwei, LING Sunbin, ZHENG Shusen, et al. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA[J]. Molecular Cancer, 2019, 18(1): 114.
[13] JOHNSON P, ZHOU Qing, DAO D Y, et al. Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma[J]. Nature Reviews Gastroenterology & Hepatology, 2022, 19(10): 670-681.
[14] MENG Zuowei, REN Qingqi, ZHONG Guolin, et al. Noninvasive detection of hepatocellular carcinoma with circulating tumor DNA features and α-fetoprotein[J]. Journal of Molecular Diagnostics, 2021, 23(9): 1174-1184.
[15] HAN H S, LEE K W. Liquid biopsy: an emerging diagnostic, prognostic, and predictive Tool in gastric cancer[J]. Journal of Gastric Cancer, 2024, 24(1): 4-28.
[16] XU Ruihua, WEI Wei, KRAWCZYK M, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma[J]. Nature Materials, 2017, 16(11): 1155-1161.
[17] OLMEDILLAS-L?PEZ S, OLIVERA-SALAZAR R,GARC?A-ARRANZ M, et al. Current and emerging applications of droplet digital PCR in oncology: an updated review[J]. Molecular Diagnosis & Therapy,2022, 26(1): 61-87.
[18] 张婷婷, 韩佳迪, 刘岩峰. 电压门控钠离子通道在肿瘤转移中的作用[J]. 国际药学研究杂志,2018,45(8): 569-574. ZHANG Tingting, HAN Jiadi, LIU Yanfeng. Role of voltage-gated sodium channel in tumor metastasis[J]. Journal of International Pharmaceutical Research, 2018,45(8): 569-574.
[19] 吴珏堃, 熊志勇, 林良奕, 等. SCNM1 在乙肝相关性肝癌中的表达及临床意义[J]. 中国病理生理杂志,2019, 35(1): 188-192. WU Juekun, XIONG Zhiyong, LIN Liangyi, et al. Expression and clinical significance of SCNM1 in hepatitis B-related hepatocellular carcinoma[J]. Chinese Journal of Pathophysiology, 2019, 35(1): 188-192.
[20] 唐巧萍, 段志强, 乔悾. 钠离子通道调节蛋白1 与肝癌患者3 年预后的相关性研究[J]. 肝脏, 2020,25(6): 610-612. TANG Qiaoping, DUAN Zhiqiang, QIAO Kong. Study on the correlation between SCNM1 and 3-year prognosis in HCC patients[J]. Chinese Hepatology,2020, 25(6): 610-612.

相似文献/References:

[1]胥　劲,何　訸,黄亨建.液体活检技术在上尿路上皮癌精准诊治中的最新应用研究进展[J].现代检验医学杂志,2021,36(04):171.[doi:10.3969/j.issn.1671-7414.2021.04.037]
　XU Jin,HE He,HUANG Heng-jian.Advances in the Application of Liquid Biopsy Technique in the PreciseDiagnosis and Treatment of Upper Urothelial Carcinoma[J].Journal of Modern Laboratory Medicine,2021,36(06):171.[doi:10.3969/j.issn.1671-7414.2021.04.037]
[2]梁 佐,仝志强,岳振华,等.ctDNA 检测在非小细胞肺癌临床诊疗应用中的最新研究进展[J].现代检验医学杂志,2024,39(02):192.[doi:10.3969/j.issn.1671-7414.2024.02.035]
　LIANG Zuo,TONG Zhiqiang,YUE Zhenhua,et al.Latest Research Progress in ctDNA Detection for Clinical Diagnosis and Treatment of Non-Small Cell Lung Cancer[J].Journal of Modern Laboratory Medicine,2024,39(06):192.[doi:10.3969/j.issn.1671-7414.2024.02.035]

备注/Memo

备注/Memo:
基金项目： 陕西省自然科学基础研究计划面上项目（项目编号：2024JC-YBMS-699）；陕西省创新能力支撑计划临床医学研究中心项目（项目编号：2021LXZX3-01）。
作者简介：王娟（1983- ），女，博士，主治医师，主要从事消化道肿瘤标志物研究，E-mail：juwa1218@126.com。
通讯作者：刘家云（1971-），男，主任医师，教授，主要从事病原微生物研究，E-mail：jiayun@fmmu.edu.cn。
更新日期/Last Update: 2024-11-15