The Diagnostic Value of MicroRNAs as a Biomarker for Hepatocellular Carcinoma: A Meta-Analysis

Background. Recently, the role of microRNAs (miRNAs) in diagnosing cancer has been attracted increasing attention. However, few miRNAs have been applied in clinical practice. The purpose of this study was to evaluate the diagnostic efficacy of miRNAs for hepatocellular carcinoma (HCC) at early stages clinically. Methods. A literature search was carried out using PubMed, Web of Science, and EMBASE databases. We explored the diagnostic value of miRNAs in distinguishing HCC from healthy individuals. The quality assessment was performed in Review Manager 5.3 software. The overall sensitivity and specificity and 95% confidence intervals (CIs) were obtained with random-effects models through Stata 14.0 software. And heterogeneity was assessed using Q test and I2 statistics. Meta-regression and subgroup analyses were conducted based on the sample, nation, quality of studies, and miRNA profiling. The publication bias was evaluated through Deeks’ funnel plot. Results. A total of 34 studies, involving in 2747 HCC patients and 2053 healthy individuals, met the inclusion criteria in the 33 included literature studies. In the summary receiver operating characteristic (sROC) curve, AUC was 0.92 (95% CI, 0.90–0.94), with 0.84 (95% CI, 0.79–0.88) sensitivity and 0.87 (95% CI, 0.83–0.90) specificity. There was no publication bias (P=0.48). Conclusion. miRNAs in vivo can be acted as a potential diagnostic biomarker for HCC, which can facilitate the early diagnosis of HCC in clinical practice.

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Evaluation of the Combined Application of AFP, AFP-L3%, and DCP for Hepatocellular Carcinoma Diagnosis: A Meta-analysis

BioMed Research International ◽

10.1155/2020/5087643 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Xueying Wang ◽

Yangyu Zhang ◽

Na Yang ◽

Hua He ◽

Xuerong Tao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Sensitivity And Specificity ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Serum Biomarkers ◽

Cochrane Library ◽

Summary Receiver Operating Characteristic ◽

Random Effects Models ◽

Combined Application

The role of α-fetoprotein (AFP) in the surveillance and diagnosis of hepatocellular carcinoma (HCC) has been questioned in recent years due to its low sensitivity and specificity. In addition to AFP, several new serum biomarkers, such as lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-gamma-carboxy prothrombin (DCP), have also been identified as useful HCC serological markers. However, the exact diagnostic value of the combinations of these biomarkers for detecting HCC in patients with liver disease remains unclear. Thus, we performed the current meta-analysis to assess performance of AFP+AFP-L3%+DCP for diagnosing HCC. Studies were systematically searched in PubMed, Embase, the Cochrane Library, CNKI, and WanFang Data databases. After full-text evaluation, 13 studies from 11 articles focusing on the combination of the three serum biomarkers for HCC detection were enrolled. Random-effects models were used due to the presence of heterogeneity. The pooled sensitivity and specificity for AFP+AFP-L3%+DCP were 88% and 79%, respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.91, and the diagnostic odds ratio (DOR) was 28.33 (95% CI 16.78-47.83). Subgroup analysis showed that the pooled sensitivity and specificity of AFP+AFP-L3%+DCP in the diagnosis of HCC versus cirrhosis patients were 0.81 and 0.82, respectively. In conclusion, the combination of AFP, AFP-L3%, and DCP may prove to be useful in the diagnosis and screening of HCC.

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Diagnosis accuracy of serum glypican-3 level in patients with hepatocellular carcinoma: a systematic review with meta-analysis

The International Journal of Biological Markers ◽

10.1177/1724600818784409 ◽

2018 ◽

Vol 33 (4) ◽

pp. 353-363 ◽

Cited By ~ 4

Author(s):

Jian Li ◽

Tiezheng Wang ◽

Boxun Jin ◽

Wenlei Li ◽

Zhenshun Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Test Performance ◽

Meta Analysis ◽

Characteristic Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Summary Receiver Operating Characteristic ◽

Random Effects Models ◽

Design Deficiencies ◽

Sensitivity Specificity

Background: Previous studies have evaluated the diagnostic value of serum glypican-3 in patients with hepatocellular carcinoma. However, the results remain inconsistent and even controversial. Thus, the aim of the present meta-analysis was to clarify the diagnostic accuracy of serum glypican-3 for hepatocellular carcinoma. Methods: A meta-analysis including 22 studies was performed with 2325 cases and 2280 controls. Relevant studies were searched in the EMBASE, PubMed, and Web of Science databases, covering relevant papers published until November 1, 2017. The quality of the studies was assessed by revised QUADAS tools. Sensitivity, specificity, and other measures were pooled and determined to evaluate the accuracy of serum glypican-3 in the diagnosis of hepatocellular carcinoma by random-effects models. Summary receiver operating characteristic curve (sROC) analysis was performed to summarize the overall test performance. Results: The results showed that the pooled overall diagnostic sensitivity, specificity, and 95% confidence interval (CI) for serum glypican-3 in the diagnosis of hepatocellular carcinoma were 68% (56-79%) and 92% (82-96.0%), respectively. Besides, the summary diagnostic odds ratio and 95% CI for glypican-3 were 23.53 (8.57-64.63). In addition, the area under sROC and 95% CI was 0.87 (0.84-0.90). The major design deficiencies of included studies were differential verification bias, and a lack of clear exclusion and inclusion criteria. Conclusions: The results of this meta-analysis suggested that serum glypican-3 was acceptable as a moderate diagnostic marker in the diagnosis of hepatocellular carcinoma compared with healthy individuals, which could elevate the sensitivity and specificity of diagnosis. Furthermore, more well-designed studies with large sample sizes are needed to show the effectiveness of glypican-3 in the differential diagnosis of hepatocellular carcinoma.

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Can Serum Glypican-3 Be a Biomarker for Effective Diagnosis of Hepatocellular Carcinoma? A Meta-Analysis of the Literature

Disease Markers ◽

10.1155/2014/127831 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Sheng-Li Yang ◽

Xiefan Fang ◽

Zao-Zao Huang ◽

Xiang-Jie Liu ◽

Zhi-Fan Xiong ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Sensitivity And Specificity ◽

Meta Analysis ◽

Diagnostic Value ◽

Healthy Individuals ◽

Subgroup Analyses ◽

Effective Diagnosis ◽

Diagnostic Index

Objective. This review is to evaluate the diagnostic value of serum GPC3 for hepatocellular carcinoma (HCC) due to conflicting results reported.Methods. NCBI PubMed and Embase were comprehensively searched for studies that have used serum GPC3 level as a diagnostic index for HCC. The quality of the included studies was assessed. Subgroup analyses were conducted to evaluate the sensitivity and specificity of GPC3 as a HCC marker. Statistical analysis was performed with the software STATA version 12.0.Results. A total of 22 studies were included. The qualities of included studies were relatively poor. Among them, 18 studies have shown that serum GPC3 is a specific biomarker for HCC, and the pooled sensitivity and specificity of these studies were 69 and 93%, respectively. The other 4 studies have reported conflicting results, which were not caused by races, infection status of HBV and HCV, or assay reagents but due to one common experimental design of enrolling liver cirrhosis patients as control subjects.Conclusions. This meta-analysis indicates that serum GPC3 is elevated in HCC patients compared with healthy individuals, but more studies are needed to evaluate its effectiveness to differentially diagnose HCC and liver cirrhosis.

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Altered central and blood glutathione in Alzheimer Disease and Mild Cognitive Impairment: a meta-analysis

10.21203/rs.3.rs-430047/v1 ◽

2021 ◽

Author(s):

Jinghan J Chen ◽

Mathura Thiyagarajah ◽

Jianmeng Song ◽

Clara Chen ◽

Nathan Herrmann ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Alzheimer Disease ◽

Publication Bias ◽

Subgroup Analysis ◽

Meta Analysis ◽

Random Effects Models ◽

Mean Differences ◽

Meta Analyses

Abstract Background: Increasing evidence implicates oxidative stress (OS) in Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of brain and blood GSH may shed light on GSH changes earlier in the disease.Aim: To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses. Method: Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using Medline, PsychInfo, and Embase (1947-June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS), and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias, respectively. Results: For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] -1.45 [-1.83, -1.06], p<0.001) and MCI (-1.15 [-1.71, -0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (-1.10 [-1.58, -0.62], z=4.46, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (-0.66 [-1.11, -0.21], p=0.025). Heterogeneity was observed throughout (I2 >85%) and not fully accounted by subgroup analysis. Egger’s test indicated risk of publication bias.Conclusion: Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.

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Meta-Analysis of Antinuclear Antibodies in the Diagnosis of Antimitochondrial Antibody-Negative Primary Biliary Cholangitis

Gastroenterology Research and Practice ◽

10.1155/2019/8959103 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Qian Zhang ◽

Zhiqiang Liu ◽

Shanshan Wu ◽

Weijia Duan ◽

Sha Chen ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Antinuclear Antibodies ◽

Meta Analysis ◽

High Specificity ◽

Diagnostic Value ◽

Cochrane Library ◽

Primary Biliary Cholangitis ◽

Summary Receiver Operating Characteristic ◽

Random Effects Models ◽

Antimitochondrial Antibody

Objective. The diagnostic value of antinuclear antibodies (ANAs) including anti-gp210 and anti-sp100 for primary biliary cholangitis/cirrhosis (PBC) has been widely reported. However, their diagnostic performances for antimitochondrial antibody- (AMA-) negative PBC were less well elucidated. Therefore, the aim of the current meta-analysis was to evaluate the diagnostic accuracy of ANAs in patients with AMA-negative PBC. Materials and Methods. Literature on the diagnostic value of biomarkers for AMA-negative PBC was systematically searched in PubMed, MEDLINE, EMBASE, and the Cochrane Library. The qualities of the retrieved studies were assessed by the Quality Assessment of Diagnostic Accuracy Studies-version 2 (QUADAS-2) scale. Pooled sensitivity and specificity of the biomarkers were calculated with random-effects models. The areas under the summary receiver operating characteristic (AUSROC) curves were used to evaluate the overall diagnostic performance of ANAs. Results. A total of 11 studies (400 AMA-negative PBC patients and 6217 controls) were finally included in the meta-analysis. ANAs had an overall sensitivity of 27% (95% CI: 20%, 35%) and specificity of 98% (95% CI: 97%, 99%). The pooled sensitivities for anti-gp210 and anti-sp100 were 23% (95% CI: 13%, 37%) and 25% (95% CI: 13%, 43%), respectively, and their specificities were 99% (95% CI: 97%, 100%) and 97% (95% CI: 93%, 98%), respectively. Conclusions. ANAs exhibited high specificity but low sensitivity and therefore could be used as reliable biomarkers to reduce the necessity of liver histology.

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Diagnostic value of RNA for hepatocellular carcinoma: a network meta-analysis

Biomarkers in Medicine ◽

10.2217/bmm-2021-0327 ◽

2021 ◽

Author(s):

Zhuo Han ◽

Keming Li ◽

Jinyu Wu ◽

Keyan Wang ◽

Cuipeng Qiu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Noncoding Rna ◽

Web Of Science ◽

Meta Analysis ◽

Circular Rna ◽

Diagnostic Value ◽

Cochrane Library ◽

Retrieval Strategy ◽

Diagnostic Efficacy

Aim: The aim of this study was to evaluate the capacity of RNA in the diagnosis of hepatocellular carcinoma (HCC). Methods: A systematic review was conducted from PubMed, Cochrane Library, EMBASE and Web of Science databases via well-designed retrieval strategy. Subsequently, the network meta-analysis was performed by the STATA software. Results: Through statistical analysis, the three hypotheses of the network meta-analysis were established. In view of these hypotheses, the diagnostic efficacy of the three markers in HCC (HCC vs healthy people) may be consistent, and the cumulative ranking results showed such a trend: circular RNA >long noncoding RNA >microRNA. Conclusion: Circular RNA may be most effective for diagnosing HCC across the three types of RNA.

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Serological tumor markers of hepatocellular carcinoma: a meta-analysis

The International Journal of Biological Markers ◽

10.5301/jbm.5000119 ◽

2015 ◽

Vol 30 (1) ◽

pp. 32-42 ◽

Cited By ~ 8

Author(s):

Tarek D. Hussein

Keyword(s):

Hepatocellular Carcinoma ◽

Sensitivity And Specificity ◽

Meta Analysis ◽

Analysis Data ◽

Significant Heterogeneity ◽

Case Control Studies ◽

Clinical Value ◽

Summary Receiver Operating Characteristic ◽

Random Effects Models ◽

Low Sensitivity

Background The clinical value of serum α-fetoprotein (AFP) to detect hepatocellular carcinoma (HCC) has been questioned due to its low sensitivity and specificity. Other than AFP, several new serum biomarkers including glypican-3 (GPC3), des-γ-carboxy prothrombin (DCP), α-L-fucosidase enzyme (AFU) and vascular endothelial growth factor (VEGF) have been identified as useful HCC markers. Material and methods A systematic search on PubMed, Web of Science and others was performed. Twenty-six case-control studies on HCC-related biomarkers published from 2000 to 2014 were included in this analysis. Data on sensitivity and specificity of tests were extracted and analyzed using the Meta-DiSc 1.4 statistical program. Fixed or random-effects models were used depending on the absence or presence of significant heterogeneity. Summary receiver operating characteristic (sROC) curves were obtained to evaluate the accuracy of the studied markers. Results The areas under the sROC curve of AFP, GPC3, DCP, AFU, VEGF and the combination of each of the last 4 markers with AFP were 0.869, 0.928, 0.832, 0.851, 0.834, 0.964, 0.972, 0.873 and 0.948, respectively. A combination of AFP+GPC3, AFP+DCP or AFP+VEGF was superior to AFP alone in detecting HCC. The area under the sROC curve of GPC3 alone was significantly higher than that of AFP, whereas the areas of DCP, AFU and VEGF were comparable to that of AFP. Conclusions GPC3, DCP, AFU and VEGF are suitable markers for HCC, and their determination with AFP may prove to be useful in the diagnosis and screening of HCC.

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Diagnostic Value of lncRNAs as Biomarker in Hepatocellular Carcinoma: An Updated Meta-Analysis

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2018/8410195 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Shilian Chen ◽

Yaqin Zhang ◽

Xuan Wu ◽

Chaoyang Zhang ◽

Guancheng Li

Keyword(s):

Hepatocellular Carcinoma ◽

Publication Bias ◽

Likelihood Ratio ◽

Meta Analysis ◽

Random Effect Model ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Diagnostic Value ◽

Diagnostic Biomarkers ◽

Funnel Plot

Some long noncoding RNAs (lncRNAs) display aberrantly high or low expression in hepatocellular carcinoma (HCC) and have the potential to serve as diagnostic biomarkers. Here, we accomplished a meta-analysis based on current studies to assess the diagnostic value of lncRNAs in HCC. Eligible literatures were systematically selected from PubMed, Web of Science, and Embase (up to January 20, 2018) according to defined inclusion and exclusion criteria. QUADAS scale was applied to the quality assessment of the included studies. Statistical analysis was performed through bivariate random-effects models based on R software. Publication bias was evaluated by funnel plot and Begg’s and Egger’s tests. 16 articles containing 2,268 cancer patients and 2,574 controls were selected for the final meta-analysis. Random effect model was used for the meta-analysis due to significant between-study heterogeneity. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 0.87(0.838-0.897), 0.829(0.794-0.86), 23.085(20.575-25.901), 4.533(4.239-4.847), and 0.176(0.166-0.186), respectively. Summary receiver operating characteristic curve (SROC) was conducted to estimate the diagnostic accuracy of lncRNAs in HCC with the area under curve (AUC) of 0.915. Subgroups analysis showed that lncRNA profiling, sample size, specimen types, and ethnicity might be the sources of heterogeneity. No publication bias existed according to funnel plot symmetry and Begg’s (P= 0.187) and Egger’s (P= 0.477) tests. In conclusion, lncRNAs can serve as potential diagnostic biomarkers of HCC with high sensitivity and specificity. In addition, lncRNAs panel from serum and plasma has a relatively high diagnostic value for HCC patients from Asia.

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Evaluation of alpha-l-fucosidase for the diagnosis of hepatocellular carcinoma based on meta-analysis

LaboratoriumsMedizin ◽

10.1515/labmed-2019-0152 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Lei Xi ◽

Chunqing Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Receiver Operating Characteristic Curves ◽

Sensitivity Specificity ◽

Review Manager

AbstractObjectivesThe main aim of the present study was to assess the diagnostic value of alpha-l-fucosidase (AFU) for hepatocellular carcinoma (HCC).MethodsStudies that explored the diagnostic value of AFU in HCC were searched in EMBASE, SCI, and PUBMED. The sensitivity, specificity, and DOR about the accuracy of serum AFU in the diagnosis of HCC were pooled. The methodological quality of each article was evaluated with QUADAS-2 (quality assessment for studies of diagnostic accuracy 2). Receiver operating characteristic curves (ROC) analysis was performed. Statistical analysis was conducted by using Review Manager 5 and Open Meta-analyst.ResultsEighteen studies were selected in this study. The pooled estimates for AFU vs. α-fetoprotein (AFP) in the diagnosis of HCC in 18 studies were as follows: sensitivity of 0.7352 (0.6827, 0.7818) vs. 0.7501 (0.6725, 0.8144), and specificity of 0.7681 (0.6946, 0.8283) vs. 0.8208 (0.7586, 0.8697), diagnostic odds ratio (DOR) of 7.974(5.302, 11.993) vs. 13.401 (8.359, 21.483), area under the curve (AUC) of 0.7968 vs. 0.8451, respectively.ConclusionsAFU is comparable to AFP for the diagnosis of HCC.

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The diagnostic value of EBV-DNA and EBV-related antibodies detection for nasopharyngeal carcinoma: a meta-analysis

Cancer Cell International ◽

10.1186/s12935-021-01862-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Weixing Liu ◽

Gui Chen ◽

Xin Gong ◽

Yingqi Wang ◽

Yaoming Zheng ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Test Performance ◽

Meta Analysis ◽

Diagnostic Value ◽

Cochrane Library ◽

Control Group ◽

Summary Receiver Operating Characteristic ◽

Ebv Dna ◽

The Difference ◽

Sensitivity Specificity

Abstract Background Numerous individual studies have investigated the diagnostic value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection for nasopharyngeal carcinoma (NPC), but the conclusions remain controversial. This meta-analysis aimed to determine the value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection in the diagnosis of NPC. Methods PROSPERO registration number: CRD42019145532. PubMed, EMBASE, Cochrane Library, and Chinese data libraries (Wanfang, CNKI, and CBM) were searched up to January 2019. The pooled sensitivity, specificity, and positive likelihood, negative likelihood, and diagnostic odds ratios were conducted in this meta-analysis. Summary receiver operating characteristic curves evaluated the test-performance global summary. Publication bias was examined by Deek’s funnel plot asymmetry test. Results Forty-seven studies with 8382 NPC patients (NPC group) and 15,089 individuals without NPC (Control group) were included in this meta-analysis. The sensitivity, specificity, positive likelihood (+ LR), negative likelihood (-LR), DOR and AUC of EBV-DNA in diagnosis of NPC were: 0.76 (95% CI 0.73–0.77), 0.96 (95% CI 0.95–0.97), 14.66 (95% CI 9.97–21.55), 0.19 (95% CI 0.13–0.28), 84 (95% CI 50.45–139.88), 0.96 (SE: 0.001), and 0.55 (95% CI 0.54–0.57), 0.96 (95% CI 0.96–0.97), 12.91 (95% CI 9.55–17.45), 0.35 (95% CI 0.29–0.43), 39.57 (95% CI 26.44–59.23), 0.94 (SE: 0.002) for the EA-IgA, and 0.85 (95% CI 0.84–0.85), 0.89 (95% CI 0.88–0.89), 6.73 (95% CI5.38–8.43), 0.17 (95% CI 0.12–0.23), 43.03 (95% CI 31.51–58.76), 0.93 (SE: 0.007) for the VCA-IgA, and 0.86 (95% CI 0.85–0.88), 0.87 (95% CI 0.88–0.90), 7.55 (95% CI 5.79–9.87), 0.16 (95% CI 0.13–0.19), 50.95 (95% CI 34.35–75.57), 0.94 (SE: 0.008) for the EBNA1-IgA, and 0.70 (95% CI 0.69–0.71), 0.94 (95% CI 0.94–0.95), 9.84 (95% CI 8.40–11.54), 0.25 (95% CI 0.21–0.31), 40.59 (95% CI 32.09–51.35), 0.95 (SE: 0.005) for the Rta-IgG. The EBV-DNA had larger AUC compared with other EBV-based antibodies (P < 0.05), while the difference between EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG was not statistically significant (P > 0.05). Conclusions EBV-DNA, VCA-IgA, EBNA1-IgA and Rta-IgG detection have high accuracy in early diagnosis NPC. In addition, EBV-DNA detection has the higher diagnosis accuracy in NPC. On the other hand, EA-IgA is suitable for the diagnosis but not NPC screening.

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