Diagnostic Value of Autoantibodies in Lung Cancer: a Systematic Review and Meta-Analysis

Background/Aims: Recently, many studies have demonstrated that various tumor-associated autoantibodies have been detected in early stages of lung cancer. Therefore, we conducted a meta-analysis to comprehensively evaluate available evidence on the diagnostic value of autoantibodies against tumor-associated antigens in lung cancer. Methods: We systematically searched PubMed, Scopus, Web of Science and other databases through 23 March 2018. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. We used the bivariate mixed-effect models to calculate pooled values of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and associated 95% confidence intervals. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deek’s funnel plot was used to detect publication bias. Results: Review of 468 candidate articles identified fifty-three articles with a total of 11,515 patients for qualitative review and meta-analysis. Pooled sensitivity, specificity and area under the SROC curve were as follows for tumor-associated autoantibodies against the following proteins: p53, 0.19, 0.98, 0.82; NY-ESO-1, 0.17, 0.98, 0.90; Survivin, 0.19, 0.99, 0.96; c-myc, 0.14, 0.98, 0.45; Cyclin B1, 0.18, 0.98, 0.91; GBU4-5, 0.07, 0.98, 0.91; CAGE, 0.14, 0.98, 0.90; p16, 0.08, 0.97, 0.91; SOX2, 0.14, 0.99, 0.93; and HuD, 0.17, 0.99, 0.82. Conclusion: Each tumor-associated autoantibody on its own showed excellent diagnostic specificity for lung cancer but inadequate sensitivity. Our results suggest that combinations or panels of tumor-associated autoantibodies may provide better sensitivity for diagnosing lung cancer, and the diagnostic accuracy of tumor-associated autoantibodies should be validated in more studies.

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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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Sensitivity and Specificity of Dickkopf-1 Protein in Serum for Diagnosing Hepatocellular Carcinoma: A Meta-Analysis

The International Journal of Biological Markers ◽

10.5301/jbm.5000101 ◽

2014 ◽

Vol 29 (4) ◽

pp. 403-410 ◽

Cited By ~ 8

Author(s):

Jie Zhang ◽

Ying Zhao ◽

Qin Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Diagnostic Accuracy ◽

Test Performance ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

Likelihood Ratios ◽

Summary Receiver Operating Characteristic ◽

Knowledge Infrastructure ◽

Combined Test ◽

Dickkopf 1

Objective This meta-analysis evaluated the diagnostic accuracy of positive serum Dickkopf-1 (DKK1) for diagnosing hepatocellular carcinoma (HCC). Material and methods Articles listed on Embase, PubMed, Wanfang, Weipu Periodical Database or the Chinese National Knowledge Infrastructure (CNKI) and published up to July 10, 2013, were searched in either English or Chinese. The pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and summary receiver operating characteristic (sROC) curve were calculated to summarize the overall test performance. Results Four articles (6 studies) provided DKK1 diagnostic data. The pooled SEN, SPE, PLR, NLR, DOR and area under the sROC curve of DKK1 for the diagnosis of HCC were 0.65 (95% confidence interval [95% CI], 0.52-0.76), 0.94 (95% CI, 0.82-0.98), 10.1 (95% CI, 3.68-27.74), 0.38 (95% CI, 0.28-0.51), 26.90 (95% CI, 10.45-69.19) and 0.84 (95% CI, 0.81-0.87), respectively. Three articles (5 studies) provided DKK1 and α-fetoprotein (AFP) combined test data. The pooled SEN, SPE, PLR, NLR, DOR and area under the sROC curve of combined detection for the diagnosis of HCC were 0.81 (95% CI, 0.76-0.85), 0.85 (95% CI, 0.78-0.91), 5.52 (95% CI, 3.76-8.10), 0.22 (95% CI, 0.19-0.27), 24.60 (95% CI, 17.69-34.19) and 0.88 (95% CI, 0.85-0.91), respectively. Conclusion Both DKK1 and DKK1 plus AFP had high diagnostic accuracy for diagnosis of HCC.

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Potential Role of MicroRNA-375 as Biomarker in Human Cancers Detection: A Meta-Analysis

BioMed Research International ◽

10.1155/2017/1875843 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Jin Yan ◽

Qiang She ◽

Xiaoran Shen ◽

Yifeng Zhang ◽

Bingtuan Liu ◽

...

Keyword(s):

Test Performance ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Circulating Microrna ◽

Cancer Type ◽

Analysis Model ◽

Summary Receiver Operating Characteristic ◽

Sensitivity Specificity

The association between circulating microRNA-375 (miR-375) expression and cancers has been studied; however, the results are inconsistent. We searched PubMed, Embase, and Web of Science for studies concerning the diagnostic value of miR-375 for cancer. The bivariate meta-analysis model was employed to summarize sensitivity, specificity, and diagnostic odds ratio (DOR) for miR-375 in the diagnosis of cancer. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were also used to check the overall test performance. A total of 645 cancer patients and 421 cancer-free individuals from 12 studies were contained in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 78% (95% confidence interval (CI): 64%–87%), the specificity was 74% (95% CI: 62%–84%), the DOR was 10.04 (95% CI: 6.01–16.77), and the AUC was 0.82 (95% CI: 0.79–0.85). In addition, we found that the diagnostic effect of miR-375 varies according to the race and cancer type. Our data suggest that miR-375 profiling has a potential to be used as a screening test for cancers but the specific race and cancer should be considered. More studies on the diagnostic value of miR-375 for cancer are needed in the future.

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Accuracy of Enzyme-Linked Immunosorbent Assays (ELISAs) in Detecting Antibodies againstMycobacterium lepraein Leprosy Patients: A Systematic Review and Meta-Analysis

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2018/9828023 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Omar Ariel Espinosa ◽

Silvana Margarida Benevides Ferreira ◽

Fabiana Gulin Longhi Palacio ◽

Denise da Costa Boamorte Cortela ◽

Eliane Ignotti

Keyword(s):

Diagnostic Accuracy ◽

Odds Ratio ◽

Meta Analysis ◽

Characteristic Curve ◽

Diagnostic Odds Ratio ◽

Cochrane Library ◽

Likelihood Ratios ◽

Summary Receiver Operating Characteristic ◽

Immunosorbent Assays ◽

Sensitivity Specificity

IgM againstMycobacterium lepraemay be detected by enzyme-linked immunosorbent assays (ELISAs) based on phenolic glycolipid I (PGL-I) or natural disaccharide octyl bovine serum albumin (ND-O-BSA) as antigens, and the IgG response can be detected by an ELISA based on lipid droplet protein 1 (LID-1). The titers of antibodies against these antigens vary with operational classification. The aim of this study was to compare the accuracy of ELISAs involving PGL-I and ND-O-BSA with that involving LID-1. We included studies that analyze multibacillary and paucibacillary leprosy cases and evaluate the diagnostic accuracy of ELISAs based on LID-1 and/or PGL-I or ND-O-BSA as antigens to measure antibody titers againstM. leprae. Studies were found via PubMed, the Virtual Health Library Regional Portal, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Índice Bibliográfico Espanhol de Ciências de Saúde, the Brazilian Society of Dermatology, National Institute for Health and Clinical Excellence, Cochrane Library, Embase (the Elsevier database), and Cumulative Index to Nursing and Allied Health Literature. The Quality Assessment of Diagnostic Accuracy Studies served as a methodological validity tool. Quantitative data were extracted using the Standards for Reporting of Diagnostic Accuracy. Sensitivity, specificity, and a diagnostic odds ratio were calculated, and a hierarchical summary receiver-operating characteristic curve and forest plots were constructed. The protocol register code for this meta-analysis is PROSPERO 2017: CRD42017055983. Nineteen studies were included. ND-O-BSA showed better overall performance in terms of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio when compared with PGL-I and LID-1. The multibacillary group showed better performance on these parameters (than the paucibacillary group did), at 94%, 99%, 129, 0.05, and 2293, respectively. LID-1 did not provide any advantage regarding the overall estimate of sensitivity in comparison with PGL-I or ND-O-BSA.

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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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Diagnostic accuracy of magnetic resonance angiography for acute pulmonary embolism - a systematic review and meta-analysis

VASA ◽

10.1024/0301-1526/a000509 ◽

2016 ◽

Vol 45 (2) ◽

pp. 149-154 ◽

Cited By ~ 2

Author(s):

Jie Li ◽

Lei Feng ◽

Jiangbo Li ◽

Jian Tang

Keyword(s):

Pulmonary Embolism ◽

Magnetic Resonance ◽

Magnetic Resonance Angiography ◽

Diagnostic Accuracy ◽

Acute Pulmonary Embolism ◽

Meta Analysis ◽

Likelihood Ratios ◽

Summary Receiver Operating Characteristic ◽

Acute Pe ◽

Limited Sensitivity

Abstract. Background: The aim of this meta-analysis was to evaluate the diagnostic accuracy of magnetic resonance angiography (MRA) for acute pulmonary embolism (PE). Methods: A systematic literature search was conducted that included studies from January 2000 to August 2015 using the electronic databases PubMed, Embase and Springer link. The summary receiver operating characteristic (SROC) curve, sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR) as well as the 95 % confidence intervals (CIs) were calculated to evaluate the diagnostic accuracy of MRA for acute PE. Meta-disc software version 1.4 was used to analyze the data. Results: Five studies were included in this meta-analysis. The pooled sensitivity (86 %, 95 % CI: 81 % to 90 %) and specificity (99 %, 95 % CI: 98 % to 100 %) demonstrated that MRA diagnosis had limited sensitivity and high specificity in the detection of acute PE. The pooled estimate of PLR (41.64, 95 % CI: 17.97 to 96.48) and NLR (0.17, 95 % CI: 0.11 to 0.27) provided evidence for the low missed diagnosis and misdiagnosis rates of MRA for acute PE. The high diagnostic accuracy of MRA for acute PE was demonstrated by the overall DOR (456.51, 95 % CI: 178.38 - 1168.31) and SROC curves (AUC = 0.9902 ± 0.0061). Conclusions: MRA can be used for the diagnosis of acute PE. However, due to limited sensitivity, MRA cannot be used as a stand-alone test to exclude acute PE.

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The role of serum periostin in the diagnosis of asthma: A meta-analysis

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200038 ◽

2020 ◽

Vol 41 (4) ◽

pp. 240-247

Author(s):

Lei Yang ◽

Qingtao Zhao ◽

Shuyu Wang

Keyword(s):

Diagnostic Accuracy ◽

Meta Analysis ◽

Characteristic Curve ◽

False Negative ◽

Summary Receiver Operating Characteristic ◽

True Negative ◽

Negative Results ◽

Noninvasive Biomarker ◽

Sensitivity Specificity ◽

Serum Periostin

Background: Serum periostin has been proposed as a noninvasive biomarker for asthma diagnosis and management. However, its accuracy for the diagnosis of asthma in different populations is not completely clear. Methods: This meta-analysis aimed to evaluate the diagnostic accuracy of periostin level in the clinical determination of asthma. Several medical literature data bases were searched for relevant studies through December 1, 2019. The numbers of patients with true-positive, false-positive, false-negative, and true-negative results for the periostin level were extracted from each individual study. We assessed the risk of bias by using Quality Assessment of Diagnostic Accuracy Studies 2. We used the meta-analysis to produce summary estimates of accuracy. Results: In total, nine studies with 1757 subjects met the inclusion criteria. The pooled estimates of sensitivity, specificity, and diagnostic odds ratios for the detection of asthma were 0.58 (95% confidence interval [CI], 0.38‐0.76), 0.86 (95% CI, 0.74‐0.93), and 8.28 (95% CI, 3.67‐18.68), respectively. The area under the summary receiver operating characteristic curve was 0.82 (95% CI, 0.79‐0.85). And significant publication bias was found in this meta‐analysis (p = 0.39). Conclusion: Serum periostin may be used for the diagnosis of asthma, with moderate diagnostic accuracy.

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Diagnostic Accuracy of Machine Learning-Based Radiomics in Grading Gliomas: Systematic Review and Meta-Analysis

Contrast Media & Molecular Imaging ◽

10.1155/2020/2127062 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Curtis K. Sohn ◽

Sotirios Bisdas

Keyword(s):

Machine Learning ◽

Diagnostic Accuracy ◽

Diagnostic Performance ◽

Meta Analysis ◽

Total Sample ◽

Low Grade ◽

Sample Sizes ◽

Summary Receiver Operating Characteristic ◽

Pubmed Database ◽

Sensitivity Specificity

Purpose. This study aimed to estimate the diagnostic accuracy of machine learning- (ML-) based radiomics in differentiating high-grade gliomas (HGG) from low-grade gliomas (LGG) and to identify potential covariates that could affect the diagnostic accuracy of ML-based radiomic analysis in classifying gliomas. Method. A primary literature search of the PubMed database was conducted to find all related literatures in English between January 1, 2009, and May 1, 2020, with combining synonyms for “machine learning,” “glioma,” and “radiomics.” Five retrospective designed original articles including LGG and HGG subjects were chosen. Pooled sensitivity, specificity, their 95% confidence interval, area under curve (AUC), and hierarchical summary receiver-operating characteristic (HSROC) models were obtained. Result. The pooled sensitivity when diagnosing HGG was higher (96% (95% CI: 0.93, 0.98)) than the specificity when diagnosing LGG (90% (95% CI 0.85, 0.93)). Heterogeneity was observed in both sensitivity and specificity. Metaregression confirmed the heterogeneity in sample sizes ( p = 0.05 ), imaging sequence types ( p = 0.02 ), and data sources ( p = 0.01 ), but not for the inclusion of the testing set ( p = 0.19 ), feature extraction number ( p = 0.36 ), and selection of feature number ( p = 0.18 ). The results of subgroup analysis indicate that sample sizes of more than 100 and feature selection numbers less than the total sample size positively affected the diagnostic performance in differentiating HGG from LGG. Conclusion. This study demonstrates the excellent diagnostic performance of ML-based radiomics in differentiating HGG from LGG.

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K-rasMutational Status in Cytohistological Tissue as a Molecular Marker for the Diagnosis of Pancreatic Cancer: A Systematic Review and Meta-Analysis

Disease Markers ◽

10.1155/2014/573783 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Jing Yang ◽

Jingjing Li ◽

Rong Zhu ◽

Huawei Zhang ◽

Yuanyuan Zheng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Diagnostic Accuracy ◽

Test Performance ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

Pancreatic Tissue ◽

Test Material ◽

Original Research ◽

Summary Receiver Operating Characteristic ◽

Diagnostic Significance

Background. More clinically meaningful diagnostic tests are needed in pancreatic cancer (PC).K-rasmutations are the most frequently acquired genetic alteration.Methods. Original research articles involving the diagnostic accuracy ofK-rasmutation detection in PC were selected. Data were presented as forest plots and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance.Results. We assessed 19 studies from 16 published articles. The reports were divided into three groups according to the process used to obtain the test material. The summary estimates for detectingK-rasstatus using an invasive method (fine needle aspiration (FNA), endoscopic retrograde cholangiopancreatography (ERCP), or surgery) were better than cytology: the pooled sensitivity was 77% (95% confidence interval (CI): 74–80%) versus 54% (95% CI: 47–61%); specificity was 88% (95% CI: 85–91%) versus 91% (95% CI: 83–96%); and diagnostic odds ratio (DOR) was 20.26 (11.40–36.03) versus 7.52 (95% CI: 2.80–20.18), respectively. When two procedures were combined, the diagnostic accuracy was markedly improved.Conclusions. The analysis ofK-rasmutations in pancreatic tissue has a promising diagnostic significance in PC. Further valuable studies are needed.

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The Diagnostic Accuracy of HE4 in Lung Cancer: A Meta-Analysis

Disease Markers ◽

10.1155/2015/352670 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Daye Cheng ◽

Ying Sun ◽

Hu He

Keyword(s):

Lung Cancer ◽

Diagnostic Accuracy ◽

Likelihood Ratio ◽

Meta Analysis ◽

Characteristic Curve ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Large Sample Size ◽

Summary Receiver Operating Characteristic ◽

Diagnosis Of Lung Cancer

The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of serum HE4 for lung cancer. We conducted a comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. A total of seven articles including 715 cases and 549 controls were included for analysis. The summary estimates for serum HE4 in the diagnosis of lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68–0.75), SPE 0.85 (95% CI: 0.81–0.88), PLR 4.68 (95% CI: 3.23–6.78), NLR 0.31 (95% CI: 0.24–0.39), and DOR 17.14 (95% CI: 9.72–30.20), and the area under the curve (AUC) was 0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the diagnosis of lung cancer. In addition, considering the high heterogeneity and potential publication bias, further studies with rigorous design and large sample size are needed in the future.

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