Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer

Choi, Soo In; Jang, Mi-Ae; Jeon, Byung Ryul; Shin, Hee Bong; Lee, You Kyoung; Lee, Yong-Wha

doi:10.3343/alm.2017.37.6.526

Cited by 13 publications

(10 citation statements)

References 14 publications

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“…There were some results from other studies consistent with our conclusion ( 8 , 42 , 73 ). For example, an original study found that serum HE4 levels in patients with any histological type of LC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and small cell lung carcinoma) were significantly increased compared with those in the control group ( 73 ). Thus, the overexpression of HE4 suggested a scientific basis for its potential diagnostic ability in LC.…”

Section: Discussionsupporting

confidence: 92%

The Role of Human Epididymis Protein 4 in the Diagnosis and Prognosis of Diseases: An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies

Sun

Yang

et al. 2022

Front. Med.

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BackgroundThe application of human epididymis protein 4 (HE4) in diverse health diseases, especially in cancers, has been extensively studied in recent decades. To summarize the existing evidence of the aforementioned topic, we conducted an umbrella review to systematically evaluate the reliability and strength of evidence regarding the role of HE4 in the diagnostic and prognostic estimate of diverse diseases.MethodsElectronic searches in PubMed, Web of Science, and Embase databases were conducted from inception to September 16, 2021, for meta-analyses, which focus on the role of HE4 in the diagnosis and prognosis of diseases. This study protocol has been registered at PROSPERO (CRD42021284737). We collected the meta-analysis effect size of sensitivity, specificity, positive predictive value, and negative predictive value from diagnostic studies and gathered the hazard ratio (HR) of disease-free survival, overall survival, and progression-free survival from prognostic studies. For each systematic review and meta-analysis, we used a measurable tool for evaluating systematic reviews and meta-analysis (AMSTAR) to evaluate the methodological quality. Additionally, we assessed the quality of evidence on estimating the ability of HE4 in the diagnosis and prognosis of diverse diseases by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline.ResultsOverall, 20 meta-analyses including a total of 331 primary studies of different diseases were examined, mainly including ovarian cancer (OC) (n = 9), endometrial cancer (EC) (n = 6), and lung cancer (LC) (n = 4). The methodological qualities of all studies were rated as moderate (45%) or high (55%) by the AMSTAR. According to the GRADE, the certainties of 18 diagnostic pieces of evidence (9 for sensitivity and 9 for specificity) were rated as moderate (34%), low (33%), and very low (33%). Moreover, outcomes from prognosis studies showed evidence (1 for disease-free survival) with high certainty in regard to cancers (such as EC, OC, and LC) with the remaining three being moderate.ConclusionThis umbrella review suggested that HE4 was a favored biomarker in the prognosis of cancers, which was supported by high certainty of evidence. Additionally, HE4 could provide a suitable method for the diagnosis of EC, OC, and LC with moderate certainty evidence. Further large prospective cohort studies are needed to better elucidate the diagnostic and prognostic role of HE4 in diseases.

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Section: Discussionsupporting

confidence: 92%

The Role of Human Epididymis Protein 4 in the Diagnosis and Prognosis of Diseases: An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies

Sun

Yang

et al. 2022

Front. Med.

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“…In combination with the relationship between these three genes and other tumors and the findings of this study, we believe that these three immune-related genes could affect the immune microenvironment of LUAD and might be involved in the occurrence and progression of LUAD. Additionally, along with further exploration, researchers found that WFDC2 presented a high expression state in lung cancer (55)(56)(57)(58) and recognized that WFDC2 as a serum tumor marker had important clinical application in the early diagnosis of lung cancer and the monitoring of a curative effect (59). Nevertheless, the expression of WFDC2 in LUAD and its relationship with patients prognosis were rarely reported.…”

Section: Discussionmentioning

confidence: 99%

A Prognostic Nomogram Combining Immune-Related Gene Signature and Clinical Factors Predicts Survival in Patients With Lung Adenocarcinoma

Song

Guo

et al. 2020

Front. Oncol.

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The existence of tumor heterogeneity and complex carcinogenic mechanisms in lung adenocarcinoma (LUAD) make the most commonly used TNM staging system unable to well-interpret the prognosis of patients. Using transcriptome profiling and clinical data from The Cancer Genome Atlas (TCGA) database, we constructed an immune signature based on a multivariate Cox analysis (stepwise model). We estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients according to the pRRophetic algorithm. Gene-set variation analysis (GSVA) was used to reveal pathway enrichment between groups. Moreover, immune microenvironment landscape was described by single-sample gene-set enrichment analysis (ssGSEA) and CIBERSORT and systematically correlated with genomic of these patients. A prognostic nomogram combining the immune signature and TNM stage to predict the prognosis was developed by multivariate Cox regression. The novel signature with four immune-related genes (MAL, MS4A1, OAS1, and WFDC2) had good robustness, which can accurately distinguish between high-and low-risk patients. Compared with low-risk patients, high-risk patients with a worse prognosis (5-year OS: 46.5 vs. 59.4%, p = 0.002) could benefit more from immunotherapy and the application of common chemotherapeutic agents such as cisplatin and paclitaxel (Wilcoxon test, all p < 0.05). There were significant differences in tumor immune microenvironment and metabolic pathways between the two groups. Additionally, the constructed nomogram had reliable predictive performance with the C-index of 0.725 (95% CI = 0.668-0.781) in the development set (n = 500), 0.793 (95% CI = 0.728-0.858) in the internal validation set (n = 250) and 0.679 (95% CI = 0.644-0.714) in the external validation set (n = 442). The corresponding calibration curves also showed good consistency. To sum up, we developed an immune-related gene signature and comprehensively evaluated LUAD immune landscape and metabolic pathways. Effective differentiation of high-and low-risk patients and accurate construction of nomogram would be helpful to the development of individualized treatment strategies.

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“…Elevation of serum HE4 levels has been reported in patients with lung cancer [28], ovarian cancer [29], and chronic kidney disease [30], and has already been applied to the diagnosis of ovarian cancer in clinical practice. Therefore, these patients were excluded from this study to avoid cofounding factors.…”

Section: Pf-ild Is a Progressive Fibrosing Phenotype With Poor Prognomentioning

confidence: 99%

Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

Nakatani

Masuo

Nukui

et al. 2021

Respiratory Investigation

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BACKGROUND The clinical course and prognosis of progressive fibrosing interstitial lung diseases (PF-ILDs) vary from individual to individual. Predictive serum biomarkers for the management of the disease are needed. Serum human epididymis protein 4 (HE4) has been reported to be elevated in patients with IPF, yet its clinical utility has not been elucidated. We evaluated whether serum HE4 could be a biomarker for patients with PF-ILD. METHODS Serum HE4 was measured in a retrospective study that consisted of 34 patients with PF-ILD and 40 healthy volunteers. The relationship between serum HE4 levels and clinical parameters or prognosis was investigated. To validate the significance of the results, a prospective observational study that consisted of 37 patients with PF-ILD and 40 control patients without PF-ILD was performed. RESULTS Serum HE4 was higher in patients with PF-ILD than in health volunteers (P < 0.01). A correlation of the serum HE4 levels with the extent of honeycombing on chest high-resolution computed tomography was identified (r = 0.41, P = 0.015). In multivariate analysis by the Cox proportional hazard model, higher HE4 levels (> 238 pmol/l) were associated with elevated mortality risk (HR 7.27, 95% CI 1.56-34.0, P = 0.01 in the derivation cohort; HR 44.3, 95% CI 4.19-468, P < 0.01 in validation cohort). CONCLUSIONS Serum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD.

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Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer

Cited by 13 publications

References 14 publications

The Role of Human Epididymis Protein 4 in the Diagnosis and Prognosis of Diseases: An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies

The Role of Human Epididymis Protein 4 in the Diagnosis and Prognosis of Diseases: An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies

A Prognostic Nomogram Combining Immune-Related Gene Signature and Clinical Factors Predicts Survival in Patients With Lung Adenocarcinoma

Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

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