Diagnostic value of circulating-tumor DNA in Chinese patients with primary liver cancer: a Meta-analysis

doi:10.3877/cma.j.issn.2095-3232.2022.06.015

Abstract

Abstract:

Objective

To systematically evaluate the diagnostic value of circulating-tumor DNA (ctDNA) in Chinese patients with primary liver cancer (PLC).

Methods

Literature related to ctDNA for the diagnosis of liver cancer were searched from PubMed, Web of Science, Embase, CNKI, Wanfang Data and Chongqing VIP databases from the inception date to November 2021. The searching terms included circulating-tumor DNA, ctDNA, free DNA, circulating DNA, cfDNA, plasma DNA, serum DNA, and liver cancer, hepatocellular carcinoma, liver tumor, primary liver cancer, etc. After data extraction and quality evaluation of the included studies, the combined sensitivity, specificity were calculated, the forest plot and summary receiver operating characteristic (sROC) curve were delineated and the area under the ROC curve (AUC) was calculated by Review Manager 5.3 and Stata 15.1 software. The heterogeneous sources were analyzed by Meta-regression analysis and subgroup analysis. The publication bias was assessed by Deek's funnel plot.

Results

25 literature were included, including 4 063 liver cancer patients and 3 509 controls. In 5 studies, quantitative analysis of the concentration of ctDNA was conducted, qualitative analysis of tumor-specific single-gene methylation in ctDNA was performed in 14 studies, and diagnostic models were constructed based on the characteristics of ctDNA in 6 studies. The combined sensitivity, specificity and AUC in the quantitative studies were 0.68(0.58-0.77), 0.82(0.71-0.89) and 0.81(0.77-0.84), 0.55(0.47-0.62), 0.99(0.93-1.00) and 0.80(0.77-0.83) in the qualitative studies, and 0.81(0.72-0.87), 0.91(0.85-0.94) and 0.93(0.90-0.95) in the model construction studies, respectively. Deek's funnel plot indicated that no significant publication bias was observed in quantitative studies (t=1.080, P>0.05), qualitative studies (t=0.690, P>0.05) and model construction studies (t=0.230, P>0.05).

Conclusions

ctDNA possesses high application value in the diagnosis of liver cancer in China. The diagnostic performance of ctDNA-based model is superior that of quantitative and qualitative analyses.

Key words: Carcinoma, hepatocellular, Circulating tumor DNA, Diagnostic test, Meta-analysis

Xinting Pan, Zhixiong Cai, Geng Chen, Xiuqing Dong, Xiaolong Liu. Diagnostic value of circulating-tumor DNA in Chinese patients with primary liver cancer: a Meta-analysis[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2022, 11(06): 607-614.

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References 42

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分组		文献数（篇）	χ²值	P值	合并敏感度		合并特异度
分组		文献数（篇）	χ²值	P值	95%CI	P值	95%CI	P值
定性研究组
样本来源			10.68	<0.01		0.04		0.13
	血浆	9			0.49（0.40~0.58）		0.99（0.96~1.00）
	血清	4			0.65（0.54~0.76）		0.98（0.95~1.00）
模型构建组
研究类型			46.32	<0.01		0.16		<0.01
	前瞻性	2			0.86（0.75~0.97）		0.78（0.64~0.92）
	回顾性	7			0.85（0.79~0.92）		0.92（0.88~0.96）
地区			43.65	<0.01		0.86		<0.01
	南方	6			0.83（0.73~0.93）		0.82（0.76~0.88）
	北方	4			0.74（0.56~0.91）		0.95（0.91~0.98）
对照类型			7.65	0.02		0.14		0.14
	健康人	5			0.80（0.69~0.92）		0.95（0.91~0.98）
	良性肝病	7			0.80（0.70~0.90）		0.86（0.81~0.92）
肝癌病例数			6.79	0.03		0.47		<0.01
	≥100例	5			0.88（0.82~0.93）		0.86（0.79~0.93）
	<100例	7			0.71（0.62~0.81）		0.94（0.89~0.98）

分组		文献数（篇）	χ²值	P值	合并敏感度		合并特异度
分组		文献数（篇）	χ²值	P值	95%CI	P值	95%CI	P值
定性研究组
样本来源			10.68	<0.01		0.04		0.13
	血浆	9			0.49（0.40~0.58）		0.99（0.96~1.00）
	血清	4			0.65（0.54~0.76）		0.98（0.95~1.00）
模型构建组
研究类型			46.32	<0.01		0.16		<0.01
	前瞻性	2			0.86（0.75~0.97）		0.78（0.64~0.92）
	回顾性	7			0.85（0.79~0.92）		0.92（0.88~0.96）
地区			43.65	<0.01		0.86		<0.01
	南方	6			0.83（0.73~0.93）		0.82（0.76~0.88）
	北方	4			0.74（0.56~0.91）		0.95（0.91~0.98）
对照类型			7.65	0.02		0.14		0.14
	健康人	5			0.80（0.69~0.92）		0.95（0.91~0.98）
	良性肝病	7			0.80（0.70~0.90）		0.86（0.81~0.92）
肝癌病例数			6.79	0.03		0.47		<0.01
	≥100例	5			0.88（0.82~0.93）		0.86（0.79~0.93）
	<100例	7			0.71（0.62~0.81）		0.94（0.89~0.98）

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