Diagnostic and prognostic role of HE4 expression in multiple carcinomas

Kumarasamy, Chellan; Madhav, Madurantakam Royam; Sabarimurugan, Shanthi; Lakhotiya, Kartik; Pandey, Venkatesh; Priyadharshini, T; Baxi, Siddhratha; Gothandam, Kodiveri Muthukaliannan; Jayaraj, Rama

doi:10.1097/md.0000000000015336

Cited by 14 publications

(7 citation statements)

References 42 publications

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“…According to the criteria of the GRADE guideline, there was one high-quality evidence, Dai et al ( 44 ) conducted a meta-analysis and reported that the HE4 level can provide a useful prognostic biomarker (only for DFS) for patients with cancers (987 patients with EC, 211 patients with LC, and 98 patients with OC). The prognostic effect of HE4 on the disease was mainly focused on OC, but a systematic review suggested that the prognostic role of HE4 in other types of cancers needed more endeavor than before ( 55 ). Previous articles or meta-analyses suggested that OC ( 23 , 56 ), EC ( 57 ), LC ( 58 ), and GC ( 59 ) patients with a high concentration of HE4 have shorter survival or more likely metastasis than those with low concentrations.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…According to the Kumarasamy et al 21 review, the possibility of using HE4 as a prognostic marker has not been adequately explored. Looking at the Lan et al 22 results, the normalization of CA125 level in serum after three cycles of chemotherapy may predict the favorable outcome of patients with advanced ovarian cancer if it was pathologic at the beginning of treatment.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and predictive value of combined HE-4 and CA-125 biomarkers during chemotherapy in patients with epithelial ovarian cancer

et al. 2020

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Introduction: At present there is no predictive value univocally associated with the success of chemotherapy. Biomarkers produced by ovarian cancer (HE4 and Ca125) could have a good prognostic significance. The aim of this study is to prove the ability of biomarkers to identify patients with the highest risk of non-optimal response during the chemotherapy, and to predict which patients will most likely develop recurrence of disease. Methods: We analyzed 78 patients with epithelial ovarian cancers who underwent surgery in the biennium 2016–2017. All the patients underwent chemotherapy after surgery or interval debulking surgery following neoadjuvant therapy. Serum levels of HE4 and Ca125 were measured at diagnosis and at each cycle of chemotherapy. We established the degree of response to the treatment by computed tomography scan, and the patients were followed up (median: 10 months). The parameters of progression-free survival and disease-free survival were related to serum levels of biomarkers. Results: Both CA125 and HE4 values became negative at the fourth cycle in the patients with good response to chemotherapy. HE4 increased earlier than Ca125. The parameters that best correlated with a long progression-free survival were: negativization of the marker after the third cycle of chemotherapy (HE4: odds ratio (OR) 5.5; Ca125: OR 9.1) and biomarker serum levels lower than the mean value in the affected population at the time of diagnosis (HE4: OR 3.4; Ca125: OR 3.7). Conclusions: We can conclude that the monitoring of HE4 and Ca125 during chemotherapy, especially at the third cycle, is recommended, because their variation is a good prognostic factor.

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“…It is highly expressed in the serum of patients with malignant tumors but may be increased in varying degrees in the serum of benign lesions or healthy patients. HE4 has been recently identified as a potential biomarker in endometrial carcinoma (3,4,27,28). Some studies (3,5,(29)(30)(31)(32)(33) showed that CA125 and HE4 were significantly correlated with histological grade, stage, lymph node metastasis, muscular invasion, and cervical involvement.…”

Section: Introductionmentioning

confidence: 99%

Combination IETA Ultrasonographic Characteristics Simple Scoring Method With Tumor Biomarkers Effectively Improves the Differentiation Ability of Benign and Malignant Lesions in Endometrium and Uterine Cavity

Lin

Zhao²,

Zhu³

et al. 2021

Front. Oncol.

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ObjectivesTo evaluate International Endometrial Tumor Analysis (IETA) ultrasonographic characteristics simple scoring method and tumor biomarkers for the diagnosis of uterine cavity and endometrial lesions.MethodsWe classified and scored the normalized description of IETA ultrasonic characteristics, according to IETA expert consensus literature, previous IETA-related research articles, and the previous research experience of this project group. We conducted a retrospective analysis of the ultrasound images of 594 patients enrolled from January 2017 to June 2020, scored them item by item, and finally calculated the total score of each case. Meanwhile, we combined the results of seven tumor biomarkers. The objective was to evaluate the sensitivity, specificity, coincidence rate, and the area under receiver operating characteristic (ROC) curve of IETA ultrasonographic characteristics simple scoring method and tumor biomarkers for benign and malignant uterine cavity or endometrial lesions. The diagnostic efficiency between the combined method and the single method was compared.ResultsA total of 594 cases were confirmed by postoperative pathology or surgery records, including 475 benign lesions and 119 malignant lesions. In the simple ultrasound scoring method, the average score of benign lesions was 3.879 ± 1.279 and that of malignant lesions was 9.676 ± 4.491. If ≥6.5 points was taken as the cutoff value for the judgment of malignant lesions, the sensitivity, specificity, coincidence rate, and the area under receiver operating characteristic (ROC) curve (AUC) were 76.5%, 96.0%, 92.1%, and 0.935, respectively. The difference in tumor antigen 19-9 (CA19-9) and human epididymal protein 4 (HE4) between benign and malignant lesions was statistically significant (all p ≤ 0.01). The other five tumor biomarkers (CA125, CA15-3, SCC-Ag, AFP, and CEA) showed no statistically significant difference in benign and malignant lesions. If the value of CA19-9 ≥13.96 U/ml was taken as cutoff value, the sensitivity, specificity, and coincidence rate of the diagnosis of endometrial benign and malignant lesions were 54.8%, 74.7%, and 70.7%, respectively, and the AUC was 0.620. If the value of HE4 ≥ 39.075 pmol/L was taken as cutoff point, the sensitivity, specificity, coincidence rate, and AUC were 77.4%, 67.9%, 69.8%, and 0.796, respectively. The sensitivity was increased to 97.6% and the AUC was 0.939 when IETA ultrasound characteristics simple scoring method combined CA19-9 and HE4 in parallel test.ConclusionsIn IETA ultrasound characteristics simple scoring method, with ≥6.5 points as the cutoff value, it could quickly and accurately assess the benign and malignant in uterine cavity and endometrial lesions, with high diagnostic value. The diagnostic efficacy of seven tumor biomarkers was all mediocre. Combining with these two methods, the comprehensive diagnosis could improve sensitivity and accuracy and reduce the risk of missed diagnosis.

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Diagnostic and prognostic role of HE4 expression in multiple carcinomas

Cited by 14 publications

References 42 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

Prognostic and predictive value of combined HE-4 and CA-125 biomarkers during chemotherapy in patients with epithelial ovarian cancer

Combination IETA Ultrasonographic Characteristics Simple Scoring Method With Tumor Biomarkers Effectively Improves the Differentiation Ability of Benign and Malignant Lesions in Endometrium and Uterine Cavity

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