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

doi:10.3969/j.issn.1674-8115.2023.09.012

Abstract

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

CLC Number:

R735.8

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.

Figures/Tables 13

TrendMD

References 40

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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)

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