细胞游离DNA在胆道癌诊断中的价值：一项meta分析

doi:10.3969/j.issn.1674-8115.2023.09.012

上海交通大学学报（医学版） ›› 2023, Vol. 43 ›› Issue (9): 1175-1185.doi: 10.3969/j.issn.1674-8115.2023.09.012

• 论著 · 循证医学 • 上一篇

细胞游离DNA在胆道癌诊断中的价值：一项meta分析

杨越¹^,²(), 何开举³, 宗家豪⁴, 杨自逸¹^,², 吴向嵩¹^,², 龚伟¹^,²()

^1.上海交通大学医学院附属新华医院普外科，上海 200092
^2.上海市胆道疾病研究重点实验室，上海交通大学医学院胆道疾病研究所，上海市胆道疾病研究中心，上海 200092
^3.上海交通大学医学院，上海 200025
^4.山东大学齐鲁医院消化内科，济南 250012

收稿日期:2023-05-30 接受日期:2023-08-22 出版日期:2023-09-28 发布日期:2023-09-28
通讯作者: 龚伟 E-mail:yueyueyoung@126.com;gongwei@xinhuamed.com.cn
作者简介:杨　越（1999—），女，硕士生；电子信箱：yueyueyoung@126.com。
基金资助:
国家自然科学基金(81974371);上海交通大学医学院“双百人”项目(20151001)

Diagnostic value of cell-free DNA to biliary tract cancers: a meta-analysis

YANG Yue¹^,²(), HE Kaiju³, ZONG Jiahao⁴, YANG Ziyi¹^,², WU Xiangsong¹^,², GONG Wei¹^,²()

^1.Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
^2.Shanghai Key Laboratory of Biliary Tract Disease Research, Research Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai Research Center of Tract Disease, Shanghai 200092, China
^3.Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
^4.Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China

Received:2023-05-30 Accepted:2023-08-22 Online:2023-09-28 Published:2023-09-28
Contact: GONG Wei E-mail:yueyueyoung@126.com;gongwei@xinhuamed.com.cn
Supported by:
National Natural Science Foundation of China(81974371);“Two-hundred Talents” Program of Shanghai Jiao Tong University School of Medicine(20151001)

摘要/Abstract

摘要：

目的·采用meta分析方法全面评价细胞游离DNA（cell-free DNA，cfDNA）对胆道癌（biliary tract cancer，BTC）的诊断准确性，探究样本来源、检测方法以及截断值选择等对诊断效果的影响，为更好开展临床应用提供依据。方法·检索8个中英文数据库中关于cfDNA对BTC诊断价值的前瞻性或回顾性研究，截止时间为2023年4月。根据纳入和排除标准进行筛选和数据提取，用Spearman秩相关分析评估阈值效应，运用Cochran Q检验、I²检验分析纳入研究间的异质性。拟合双变量混合效应模型，计算总体敏感度、特异度和曲线下面积（area under the curve，AUC）等统计量，判断诊断性能。同时，基于研究类型、样本量大小、检测方式、样本来源和诊断参照标准进行亚组分析。结果·共纳入28项诊断性试验，用诊断性试验准确性质量评价工具2（Diagnostic Accuracy Studies Tool Version 2，QUADAS-2）评价均属于中-高等质量研究，Spearman秩相关分析提示存在阈值效应，合并统计量后求得敏感度（Sen_合并）为0.80（95%CI 0.67~0.88），特异度（Spe_合并）为0.96（95%CI 0.92~0.98），阳性似然比（PLR_合并）为22.7（95%CI 9.4~55.2），阴性似然比（NLR_合并）为0.21（95%CI 0.12~0.36），诊断比数比（DOR_合并）为108（95%CI 31~374）。综合受试者工作特征（summary receiver operating characteristic，SROC）曲线的AUC为0.96（95%CI 0.94~0.98），提示cfDNA对BTC的诊断效能较高。亚组分析结果提示，选择不同的检测方式和样本来源的准确度和敏感度有所不同。结论·cfDNA检测对诊断BTC敏感度和特异度较高，适用于经影像学和常规肿瘤标志物初筛怀疑有恶性风险的患者，但检测方法和样本来源的选择仍需进一步开展面向更广泛人群的临床研究来进一步规范。

关键词: meta分析, 胆道癌, 细胞游离DNA, 诊断

Abstract:

Objective ·To comprehensively evaluate the diagnostic accuracy of cell-free DNA (cfDNA) to biliary tract cancer (BTC), and provide a basis for better clinical application. Methods ·Clinical studies on the diagnostic value of cfDNA to BTC were collected by searching eight databases from inception to April 2023. The studies were selected according to the inclusion and exclusion criteria, and then data was extracted. The threshold effects were assessed with Spearman′s rank correlation analysis, and heterogeneity among the included studies was analyzed by using Cochran′s Q test and I² test. A bivariate mixed-effects model was fitted, and statistics such as overall sensitivity, specificity, and area under the curve (AUC) were calculated to determine the diagnostic performance. The subgroup analyses were carried out based on the study type, sample size, detection method, sample source, and diagnostic reference standard. Results ·A total of 28 diagnosis tests were included, all of which were evaluated as medium-high quality by using Diagnostic Accuracy Studies Tool Version 2 (QUADAS-2). The presence of threshold effects was found by using the Spearman rank correlation analysis. The pooled sensitivity was 0.80 (95%CI 0.67?0.88), and specificity was 0.96 (95%CI 0.92?0.98), positive likelihood ratio (PLR) was 22.7 (95%CI 9.4?55.2), negative likelihood ratio (NLR) was 0.21 (95%CI 0.12?0.36), and diagnostic odds ratio (DOR) was 108 (95%CI 31?374), respectively. The AUC of the summary receiver operating characteristic (SROC) curve was 0.96 (95%CI 0.94?0.98), demonstrating the high accuracy of cfDNA in the diagnosis of BTC. The results of subgroup analyses suggested that the accuracy and sensitivity of choosing different testing methods and sample sources varied. Conclusion ·The detection of cfDNA has high sensitivity and specificity in diagnosing BTC, and is suitable for the patients suspected to be malignant after screening with imaging tests and conventional tumor markers. However, the standardization and uniformity of detection methods and sample sources still need to be further standardized by conducting clinical studies on a wider population.

Key words: meta-analysis, biliary tract cancer (BTC), cell-free DNA (cfDNA), diagnosis

中图分类号:

R735.8

杨越, 何开举, 宗家豪, 杨自逸, 吴向嵩, 龚伟. 细胞游离DNA在胆道癌诊断中的价值：一项meta分析[J]. 上海交通大学学报（医学版）, 2023, 43(9): 1175-1185.

YANG Yue, HE Kaiju, ZONG Jiahao, YANG Ziyi, WU Xiangsong, GONG Wei. Diagnostic value of cell-free DNA to biliary tract cancers: a meta-analysis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(9): 1175-1185.

图/表 13

参考文献 40

1	VALLE J W, LAMARCA A, GOYAL L, et al. New horizons for precision medicine in biliary tract cancers[J]. Cancer Discov, 2017, 7(9): 943-962.
2	RIZVI S, KHAN S A, HALLEMEIER C L, et al. Cholangiocarcinoma: evolving concepts and therapeutic strategies[J]. Nat Rev Clin Oncol, 2018, 15(2): 95-111.
3	BENAVIDES M, ANTÓN A, GALLEGO J, et al. Biliary tract cancers: seom clinical guidelines[J]. Clin Transl Oncol, 2015, 17(12): 982-987.
4	EVERHART J E, RUHL C E. Burden of digestive diseases in the United States Part Ⅲ: liver, biliary tract, and pancreas[J]. Gastroenterology, 2009, 136(4): 1134-1144.
5	WAN J C M, MASSIE C, GARCIA-CORBACHO J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA[J]. Nat Rev Cancer, 2017, 17(4): 223-238.
6	VALLE J W, KELLEY R K, NERVI B, et al. Biliary tract cancer[J]. Lancet, 2021, 397(10272): 428-444.
7	BANALES J M, MARIN J J G, LAMARCA A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(9): 557-588.
8	ROA J C, GARCÍA P, KAPOOR V K, et al. Gallbladder cancer[J]. Nat Rev Dis Primers, 2022, 8(1): 69.
9	梁后杰, 秦叔逵, 沈锋, 等. CSCO胆道系统肿瘤诊断治疗专家共识(2019年版)[J]. 临床肿瘤学杂志, 2019, 24(9): 828-838.
	LIANG H J, QIN S K, SHEN F et al. Expert consensus on diagnosis and treatment of CSCO biliary systerm tumors (2019 edition)[J]. Chinese Clinical Oncology, 2019, 24(9): 828-838.
10	VALLE J W. Advances in the treatment of metastatic or unresectable biliary tract cancer[J]. Ann Oncol, 2010, 21(Suppl 7): vii345-vii348.
11	BLECHACZ B, KOMUTA M, ROSKAMS T, et al. Clinical diagnosis and staging of cholangiocarcinoma[J]. Nat Rev Gastroenterol Hepatol, 2011, 8(9): 512-522.
12	蔡晨, 龚伟. 胆囊癌辅助治疗的研究进展[J]. 外科理论与实践, 2021, 26(2): 167-170.
	CAI C, GONG W. Study on gallbladder cancer adjuvant therapy[J]. Surgery Theory and Practice, 2021, 26(2): 167-170.
13	LONE S N, NISAR S, MASOODI T, et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments[J]. Mol Cancer, 2022, 21(1): 79.
14	CROWLEY E, DI NICOLANTONIO F, LOUPAKIS F, et al. Liquid biopsy: monitoring cancer-genetics in the blood[J]. Nat Rev Clin Oncol, 2013, 10(8): 472-484.
15	ALIX-PANABIÈRES C, PANTEL K. Liquid biopsy: from discovery to clinical application[J]. Cancer Discov, 2021, 11(4): 858-873.
16	LEON S A, SHAPIRO B, SKLAROFF D M, et al. Free DNA in the serum of cancer patients and the effect of therapy[J]. Cancer Res, 1977, 37(3): 646-650.
17	VESSIES D C L, GREUTER M J E, VAN ROOIJEN K L, et al. Performance of four platforms for KRAS mutation detection in plasma cell-free DNA: ddpcr, Idylla, COBAS z480 and BEAMing[J]. Sci Rep, 2020, 10(1): 8122.
18	HEITZER E, ULZ P, GEIGL J B. Circulating tumor DNA as a liquid biopsy for cancer[J]. Clin Chem, 2015, 61(1): 112-123.
19	OLMEDILLAS-LÓPEZ S, GARCÍA-ARRANZ M, GARCÍA-OLMO D. Current and emerging applications of droplet digital PCR in oncology[J]. Mol Diagn Ther, 2017, 21(5): 493-510.
20	IGNATIADIS M, SLEDGE G W, JEFFREY S S. Liquid biopsy enters the clinic: implementation issues and future challenges[J]. Nat Rev Clin Oncol, 2021, 18(5): 297-312.
21	SIRAVEGNA G, MUSSOLIN B, VENESIO T, et al. How liquid biopsies can change clinical practice in oncology[J]. Ann Oncol, 2019, 30(10): 1580-1590.
22	SHEN N J, ZHANG D D, YIN L, et al. Bile cell‑free DNA as a novel and powerful liquid biopsy for detecting somatic variants in biliary tract cancer[J]. Oncol Rep, 2019, 42(2): 549-560.
23	央茂, 李永盛, 吴文广, 等. 液态活检技术在胆道肿瘤诊治中的应用进展[J]. 中华肝胆外科杂志, 2021, 27(6): 472-476.
	YANG M, LI Y S, WU W G et al. Application progress of liquid biopsy in the diagnosis and treatment of biliary tract cancer[J]. Chinese Journal of Hepatobiliary Surgery, 2021, 27(6): 472-476.
24	LIBERATI A, ALTMAN D G, TETZLAFF J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration[J]. BMJ, 2009, 339: b2700.
25	HAN J Y, AHN K S, KIM T S, et al. Liquid biopsy from bile-circulating tumor DNA in patients with biliary tract cancer[J]. Cancers, 2021, 13(18): 4581.
26	HE S, ZENG F X, YIN H H, et al. Molecular diagnosis of pancreatobiliary tract cancer by detecting mutations and methylation changes in bile samples[J]. EClinicalMedicine, 2023, 55: 101736.
27	HUA Y, SUN F Y, HU F, et al. Diagnostic value of quantification of circulating free DNA for gall bladder cancer using a chemiluminescence DNA biosensor system based on DNA G-quadruplex/hemin enzyme[J]. Transl Oncol, 2021, 14(1): 100928.
28	KINUGASA H, NOUSO K, AKO S, et al. Liquid biopsy of bile for the molecular diagnosis of gallbladder cancer[J]. Cancer Biol Ther, 2018, 19(10): 934-938.
29	KUMARI S, HUSAIN N, AGARWAL A, et al. Diagnostic value of circulating free DNA integrity and global methylation status in gall bladder carcinoma[J]. Pathol Oncol Res, 2019, 25(3): 925-936.
30	KUMARI S, MISHRA S, HUSAIN N, et al. Comparison of circulating DNA in malignant neoplasia from diverse locations: investigating a diagnostic role[J]. Indian J Pathol Microbiol, 2022, 65(1): 93-99.
31	KUMARI S, TEWARI S, HUSAIN N, et al. Quantification of circulating free DNA as a diagnostic marker in gall bladder cancer[J]. Pathol Oncol Res, 2017, 23(1): 91-97.
32	WANG X, FU X H, QIAN Z L, et al. Non-invasive detection of biliary tract cancer by low-coverage whole genome sequencing from plasma cell-free DNA: a prospective cohort study[J]. Transl Oncol, 2021, 14(1): 100908.
33	WASENANG W, CHAIYARIT P, PROUNGVITAYA S, et al. Serum cell-free DNA methylation of OPCML and HOXD9 as a biomarker that may aid in differential diagnosis between cholangiocarcinoma and other biliary diseases[J]. Clin Epigenetics, 2019, 11(1): 39.
34	WINTACHAI P, LIM J Q, TECHASEN A, et al. Diagnostic and prognostic value of circulating cell-free DNA for cholangiocarcinoma[J]. Diagnostics, 2021, 11(6): 999.
35	莫迪, 李梦雨, 李华洋, 等. CA199、CEA及cfDNA的联合检测对胆管癌的辅助诊断价值[J]. 牡丹江医学院学报, 2020, 41(3): 18-21.
	MO D, LI M Y, LI H Y, et al. Diagnostic value of combined detection of CA, CEA and plasma cell-free DNA for cholangiocarcinoma[J]. Journal of Mudanjiang Medical University, 2020, 41(3): 18-21.
36	张俊, 徐志伟, 李克. 诊断性试验meta分析的效应指标评价[J]. 中国循证医学杂志, 2013, 13(7): 890-895.
	ZHANG J, XU Z W, LI K. Evaluation on the effect index of diagnostic test[J]. Chinese Journal of Evidence-Based Medicine, 2013, 13(7): 890-895.
37	KHAN S A, TAVOLARI S, BRANDI G. Cholangiocarcinoma: epidemiology and risk factors[J]. Liver Int, 2019, 39(S1): 19-31.
38	ARRICHIELLO G, NACCA V, PARAGLIOLA F, et al. Liquid biopsy in biliary tract cancer from blood and bile samples: current knowledge and future perspectives[J]. Explor Target Antitumor Ther, 2022, 3(3): 362-374.
39	SINGH A, DWIVEDI A. Circulating miRNA and cell-free DNA as a potential diagnostic tool in early detection of biliary tract cancer: a meta-analysis[J]. Biomarkers, 2022, 27(5): 399-406.
40	龚伟, 吴向嵩, 杨自逸. 胆囊癌转化治疗模式探索与思考[J]. 中国实用外科杂志, 2022, 42(2): 163-166.
	GONG W, WU X S, YANG Z Y. Exploring novel therapeutic approach for advanced gallbladder cancer[J]. Chinese Journal of Practical Surgery, 2022, 42(2): 163-166.

Study	Study type	Country	Reference standard
HAN 2021^[25]	Prospective study	South Korea	BTC: pathological examination
HE 2023^[26]	Retrospective and prospective study	China	BTC: pathological examination; BBD: pathological examination and clinical follow-up; healthy population: pathological examination/clinical follow-up
HUA 2021^[27]	Prospective study	China	BTC: pathological examination
KINUGASA 2018^[28]	Prospective study	Japan	Pathological examination
KUMARI 2019^[29]	Retrospective study	India	Imaging/pathological examination
KUMARI 2022^[30]	Retrospective study	India	Imaging/pathological examination
KUMARI 2017^[31]	Retrospective study	India	Imaging/pathological examination
WANG 2021^[32]	Prospective study	China	Pathological examination
WASENANG 2019^[33]	Prospective study	Thailand	BTC: pathological examination
WINTACHAI 2021^[34]	Retrospective study	Thailand	Pathological examination
MO 2020^[35]	Retrospective study	China	BTC/BBD: imaging examination/pathological examination

Study	Study type	Country	Reference standard
HAN 2021^[25]	Prospective study	South Korea	BTC: pathological examination
HE 2023^[26]	Retrospective and prospective study	China	BTC: pathological examination; BBD: pathological examination and clinical follow-up; healthy population: pathological examination/clinical follow-up
HUA 2021^[27]	Prospective study	China	BTC: pathological examination
KINUGASA 2018^[28]	Prospective study	Japan	Pathological examination
KUMARI 2019^[29]	Retrospective study	India	Imaging/pathological examination
KUMARI 2022^[30]	Retrospective study	India	Imaging/pathological examination
KUMARI 2017^[31]	Retrospective study	India	Imaging/pathological examination
WANG 2021^[32]	Prospective study	China	Pathological examination
WASENANG 2019^[33]	Prospective study	Thailand	BTC: pathological examination
WINTACHAI 2021^[34]	Retrospective study	Thailand	Pathological examination
MO 2020^[35]	Retrospective study	China	BTC/BBD: imaging examination/pathological examination

Subgroup	Study/n	Sensitivity (95%CI)	Specificity (95%CI)	PLR	NLR	DOR	AUC (95%CI)
Overall	28	0.80 (0.67‒0.88)	0.96 (0.92‒0.98)	22.7	0.21	108	0.96 (0.94‒0.98)
Study type
Prospective study	16	0.74 (0.51‒0.89)	0.97 (0.93‒0.99)	26.1	0.26	99	0.97 (0.95‒0.98)
Retrospective study	10	0.86 (0.72‒0.93)	0.93 (0.73‒0.99)	12.4	0.15	81	0.95 (0.92‒0.96)
Sample size
>90	12	0.89 (0.78‒0.95)	0.96 (0.83‒0.99)	20.9	0.12	179	0.96 (0.94‒0.98)
≤90	16	0.67 (0.47‒0.83)	0.97 (0.92‒0.99)	23.9	0.34	71	0.96 (0.94‒0.97)
Method
Gene or mutation analysis	6	0.67 (0.44‒0.84)	1.00 (0.85‒1.00)	457.0	0.33	1 394	0.95 (0.93‒0.97)
qPCR	13	0.94 (0.84‒0.98)	0.98 (0.88‒1.00)	38.8	0.06	644	0.99 (0.98‒1.00)
Methylation analysis	9	0.51 (0.37‒0.65)	0.94 (0.82‒0.98)	9.2	0.52	18	0.77 (0.73‒0.81)
Sample type
Bile	4	0.70 (0.53‒0.83)	1.00 (0.67‒1.00)	511.0	0.30	1 690	0.95 (0.92‒0.96)
Serum	19	0.85 (0.66‒0.94)	0.97 (0.90‒0.99)	24.7	0.16	156	0.97 (0.96‒0.99)
Plasma	5	0.72 (0.45‒0.89)	0.92 (0.70‒0.98)	9.4	0.30	31	0.91 (0.88‒0.93)
Control type
Benign biliary disease	18	0.68 (0.54‒0.79)	0.96 (0.92‒0.99)	19.0	0.34	57	0.93 (0.91‒0.95)
Healthy population	6	1.00 (0.70‒1.00)	1.00 (0.90‒1.00)	503.6	0.00	205 953	1.00 (0.99‒1.00)
Reference standard
Pathological examination	4	0.82 (0.69‒0.90)	0.93 (0.60‒0.99)	12.3	0.19	63	0.90 (0.87‒0.93)
Pathological examination in BTC group	16	0.75 (0.52‒0.89)	0.98 (0.94‒0.99)	33.7	0.26	130	0.98 (0.96‒0.99)
Clinical assessment	8	0.87 (0.66‒0.96)	0.95 (0.68‒0.99)	18.2	0.14	129	0.96 (0.94‒0.97)

Subgroup	Study/n	Sensitivity (95%CI)	Specificity (95%CI)	PLR	NLR	DOR	AUC (95%CI)
Overall	28	0.80 (0.67‒0.88)	0.96 (0.92‒0.98)	22.7	0.21	108	0.96 (0.94‒0.98)
Study type
Prospective study	16	0.74 (0.51‒0.89)	0.97 (0.93‒0.99)	26.1	0.26	99	0.97 (0.95‒0.98)
Retrospective study	10	0.86 (0.72‒0.93)	0.93 (0.73‒0.99)	12.4	0.15	81	0.95 (0.92‒0.96)
Sample size
>90	12	0.89 (0.78‒0.95)	0.96 (0.83‒0.99)	20.9	0.12	179	0.96 (0.94‒0.98)
≤90	16	0.67 (0.47‒0.83)	0.97 (0.92‒0.99)	23.9	0.34	71	0.96 (0.94‒0.97)
Method
Gene or mutation analysis	6	0.67 (0.44‒0.84)	1.00 (0.85‒1.00)	457.0	0.33	1 394	0.95 (0.93‒0.97)
qPCR	13	0.94 (0.84‒0.98)	0.98 (0.88‒1.00)	38.8	0.06	644	0.99 (0.98‒1.00)
Methylation analysis	9	0.51 (0.37‒0.65)	0.94 (0.82‒0.98)	9.2	0.52	18	0.77 (0.73‒0.81)
Sample type
Bile	4	0.70 (0.53‒0.83)	1.00 (0.67‒1.00)	511.0	0.30	1 690	0.95 (0.92‒0.96)
Serum	19	0.85 (0.66‒0.94)	0.97 (0.90‒0.99)	24.7	0.16	156	0.97 (0.96‒0.99)
Plasma	5	0.72 (0.45‒0.89)	0.92 (0.70‒0.98)	9.4	0.30	31	0.91 (0.88‒0.93)
Control type
Benign biliary disease	18	0.68 (0.54‒0.79)	0.96 (0.92‒0.99)	19.0	0.34	57	0.93 (0.91‒0.95)
Healthy population	6	1.00 (0.70‒1.00)	1.00 (0.90‒1.00)	503.6	0.00	205 953	1.00 (0.99‒1.00)
Reference standard
Pathological examination	4	0.82 (0.69‒0.90)	0.93 (0.60‒0.99)	12.3	0.19	63	0.90 (0.87‒0.93)
Pathological examination in BTC group	16	0.75 (0.52‒0.89)	0.98 (0.94‒0.99)	33.7	0.26	130	0.98 (0.96‒0.99)
Clinical assessment	8	0.87 (0.66‒0.96)	0.95 (0.68‒0.99)	18.2	0.14	129	0.96 (0.94‒0.97)

[1]	陈惠, 朱唯一, 姚屹瑾. 调整左旋甲状腺素治疗剂量对甲状腺功能减退孕妇母婴结局影响的meta分析[J]. 上海交通大学学报（医学版）, 2023, 43(7): 906-915.
[2]	王颖雯, 李小玲, 代佳佳, 刘芳, 黄剑峰, 王立波, 张晓波, 冯瑞. 儿童重症支气管哮喘的流行病学特征及危险因素：一项单中心前瞻性队列研究[J]. 上海交通大学学报（医学版）, 2023, 43(6): 665-672.
[3]	党向阳, 唐雨一, 李卫国, 刘恩梅. 呼出气一氧化氮检测对儿童咳嗽变异性哮喘诊断价值的系统评价和meta分析[J]. 上海交通大学学报（医学版）, 2023, 43(6): 680-688.
[4]	李瑛, 谭阳霞, 尹虹心, 蒋雁翎, 陈立, 蒙国宇. ZNF384融合亚型急性白血病的发病机制及预后研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(5): 631-640.
[5]	马卓然, 袁安彩, 蒋惠如, 陈潇雨, 张薇, 卜军. 脂质蓄积指数与中国成年人高血压关系的meta分析[J]. 上海交通大学学报（医学版）, 2023, 43(4): 466-473.
[6]	梁妍景, 黄楚贤, 李红艳, 侯黎莉. 维生素E对放疗或化疗导致的口腔黏膜炎有效性的meta分析[J]. 上海交通大学学报（医学版）, 2023, 43(2): 208-214.
[7]	冯佳丽, 彭宇, 段君凯. 川崎病相关微RNA的功能机制及生物标志物研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(2): 256-260.
[8]	后书敏, 邵静波. TdT阴性的淋巴母细胞淋巴瘤/急性淋巴细胞白血病临床特点、诊断及预后研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(1): 120-124.
[9]	杨玲, 侯黎莉, 赵燕, 陈卫宏, 张金凤, 毛艳. 口腔癌患者张口受限患病率的meta分析[J]. 上海交通大学学报（医学版）, 2023, 43(1): 61-69.
[10]	方芳, 台瑞, 余倩, 章雅青. 预康复对胃肠道择期手术患者术后恢复效果的系统评价[J]. 上海交通大学学报（医学版）, 2023, 43(1): 70-78.
[11]	何冬梅, 杨驰. 下颌骨髁突骨折的诊治方案：基于上海交通大学医学院附属第九人民医院颞下颌关节中心的经验[J]. 上海交通大学学报（医学版）, 2022, 42(6): 695-701.
[12]	何冬梅, 杨驰. 颞下颌关节强直的诊治方案：基于上海交通大学医学院附属第九人民医院颞下颌关节中心的经验[J]. 上海交通大学学报（医学版）, 2022, 42(6): 702-708.
[13]	张善勇, 杨驰. 颞下颌关节骨关节炎的诊治方案：基于上海交通大学医学院附属第九人民医院颞下颌关节中心的经验[J]. 上海交通大学学报（医学版）, 2022, 42(6): 709-716.
[14]	吕拥芬, 李嫔. 21-羟化酶缺乏症的分子诊断及临床意义[J]. 上海交通大学学报（医学版）, 2022, 42(5): 557-561.
[15]	陈卫宏, 侯黎莉, 杨玲, 毛艳, 张金凤. 冷冻疗法预防头颈癌患者放射性口腔黏膜炎的meta分析[J]. 上海交通大学学报（医学版）, 2022, 42(5): 635-645.

细胞游离DNA在胆道癌诊断中的价值：一项meta分析

Diagnostic value of cell-free DNA to biliary tract cancers: a meta-analysis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 13

参考文献 40

相关文章 15

编辑推荐

Metrics

Study	Sample	Method	Sample size/n	Cut off	TP/n	FP/n	FN/n	TN/n
HAN 2021^[25]	Bile	ddPCR	46	1 500 copies·mL^-1	20	0	22	4
HAN 2021^[25]	Plasma	ddPCR	20	60 copies·mL^-1	3	0	13	4
HE 2023^[26]	Bile	qPCR	188	NA	74	0	21	93
HE 2023^[26]	Bile	NGS	188	NA	80	2	15	91
HUA 2021^[27]	Serum	qPCR	158	403.65 ng·mL^-1	78	2	5	73
	Serum	qPCR	153	113.82 ng·mL^-1	83	0	0	70
	Serum	qPCR	158	364 ng·mL^-1	76	7	7	68
	Serum	qPCR	153	96 ng·mL^-1	83	0	0	70
KINUGASA 2018^[28]	Bile	NGS	43	NA	14	0	10	19
KUMARI 2019^[29]	Serum	qPCR	96	406.582 5 ng·mL^-1	48	5	12	31
	Serum	qPCR	96	1 128.429 ng·mL^-1	43	12	17	24
	Serum	qPCR	96	cfDNA integrity index: 0.356	47	7	13	29
	Serum	Methylated DNA Quantification Kit	96	Global DNA methylation: 0.713 5	33	18	27	18
KUMARI 2022^[30]	Serum	qPCR	75	251.2 ng·mL^-1	50	0	0	25
KUMARI 2017^[31]	Serum	qPCR	56	372.92 ng·mL^-1	30	0	4	22
KUMARI 2017^[31]	Serum	qPCR	51	218.55 ng·mL^-1	34	0	0	17
WANG 2021^[32]	Plasma	Low-coverage WGS	47	\|Z\|-score in UCAD test 2.32	26	2	3	16
WASENANG 2019^[33]	Serum	MSP	80	OPCML 3.24%‒50% methylation	32	4	8	36
	Serum	MSP	80	HOXD9 1.56%‒50% methylation	27	4	13	36
	Serum	MSP	80	HOXA9 1.56%‒50% methylation	19	15	21	25
	Serum	MSP	80	OPCML, HOXD9 both methylated	25	0	15	40
	Serum	MSP	80	OPCML, HOXA9 both methylated	12	1	28	39
	Serum	MSP	80	HOXA9, HOXD9 both methylated	10	1	30	39
	Serum	MSP	80	OPCML, HOXA9, HOXD9 ≥2 markers methylated	29	2	11	38
	Serum	MSP	80	OPCML, HOXA9, HOXD9 all methylated	9	0	31	40
WINTACHAI 2021^[34]	Plasma	qPCR	92	0.217 5 ng·µL^-1	55	1	7	29
WINTACHAI 2021^[34]	Plasma	qPCR	95	0.338 8 ng·µL^-1	51	14	11	19
MO 2020^[35]	Plasma	qPCR	85	18.06 ng·µL^-1	26	2	19	38