Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis

Abstract

Purpose A meta‐analysis was formulated to appraise the diagnostic accuracy of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC). Materials and Methods We enrolled all relevant studies published until September 2019. Four primary subgroups were investigated: the subgroup of quantitative or qualitative analysis of ctDNA, the subgroup of Ras association domain family 1 isoform A （RASSF1A） methylation in ctDNA and the subgroup of the combined alpha‐fetoprotein (AFP) and ctDNA assay. We analyzed the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) as well as the area under the curve (AUC). Results A total of 33 qualified articles with 4113 subjects were incorporated into our meta‐analysis. The combined SEN, SPE, and DOR in quantitative studies were 0.722 (95% confidence interval (95% CI): 0.686‐0.756), 0.823 (95% CI: 0.789‐0.854), 18.532 (95% CI: 8.245‐41.657), respectively, yielding an AUC of 0.880. For qualitative studies, the corresponding value was 0.568 (95% CI: 0.548‐0.587), 0.882 (95% CI: 0.867‐0.897), 10.457 (95% CI: 7.270‐15.040) and 0.787, respectively. Detection of RASSF1A methylation yielded an AUC of 0.841, with a SEN of 0.644 (95% CI: 0.608‐0.678) and a SPE of 0.875 (95% CI: 0.847‐0.900). AFP combined with ctDNA assay achieved an AUC of 0.944, with a SEN of 0.760 (95% CI: 0.728‐00.790) and a SPE of 0.920 (95% CI: 0.893‐00.942). Conclusion Circulating tumor DNA displays a promising diagnostic potential in HCC. However, it is not independently sufficient and can serve as an assistant tool combined with AFP for HCC screening and detection.

Overexpression of PKMYT1 Facilitates Tumor Development and Is Correlated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

“…Kaplan-Meier plots with log-rank tests were applied to evaluate the association between overall survival (OS) of patients with ccRCC and PKMYT1 expression. A receiver operating characteristic curve (ROC) with areas under the curve (AUC) was formulated to assess the diagnostic efficiency of PKMYT1 in ccRCC [ 34 , 35 ]. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) to estimate the prognostic effect of PKMYT1 in ccRCC.…”

“…A nomogram was developed with the “rms” R package to estimate the probability of 3-, 5-, and 10-year OS in patients with ccRCC. A concordance index (C-index) and calibration plot were applied to evaluate the nomogram discrimination and the consistence between nomogram prediction and practical observation, respectively [ 34 , 35 ]. The time-dependent ROC curves were applied to evaluate the predictive capability of the nomogram, PKMYT1 expression level, and additional clinicopathologic variables for 3-, 5-, and 10-year OS.…”

<p>A Novel lncRNA NONHSAT053785 Acts as an Independent Risk Factor for Intrahepatic Metastasis of Hepatocellular Carcinoma</p>

“…Interestingly, the AUC of AFP (0.960) in our study was much higher than the previously reported range (AUC: 0.64-0.77). [18][19][20] This phenomenon could be due to the fact that most of our patients were at the advanced stage of HCC, and therefore, presented significantly elevated levels of AFP. The ROC curve for NONHSAT053785 showed a promising AUC value of 0.801, with a sensitivity of 73.2% and a specificity of 75.4%.…”

Immune landscape and a promising immune prognostic model associated with TP53 in early‐stage lung adenocarcinoma

“…Moreover, a staggering proportion (57%) of LUAD cases initially diagnosed with metastatic neoplasm achieves a 5‐year survival rate of merely 5% 6 . Conversely, low‐dose computerized tomography (CT) is conducive to the rapid screening of early‐stage LUAD 7,8 . Those with localized tumor exhibit a relatively desirable 5‐year survival rate of up to 83% (TNM stage IA) and 71% (TNM stage IB) 9 .…”