HE4 Levels Research Articles

The Role of HE4 in the Follow-Up of Advanced Ovarian, Fallopian Tube, and Primary Peritoneal Cancer—CEEGOG OX-01 Study

Background: Ovarian, fallopian tube, and primary peritoneal cancers often share clinical characteristics and are typically diagnosed at advanced stages due to nonspecific symptoms. The utility of tumor markers, particularly CA125 and HE4, in the diagnosis and follow-up of these cancers remains an area of active investigation. Objectives: The CEEGOG (Central and Eastern European Gynecologic Oncology Group) OX-01 study aimed to evaluate HE4’s role alongside CA125 in follow-up for advanced-stage ovarian, fallopian tube, and primary peritoneal cancers. It assessed the potential for detecting recurrence using marker elevation and imaging methods, examining the necessity of dynamic monitoring and current cut-off values’ accuracy for early relapse detection. Methods: In this multicenter prospective cohort study, 117 eligible patients with Stage III–IV cancers were included. Patients had elevated CA125 or HE4 at diagnosis and achieved complete remission after first-line treatment. HE4 and CA125 levels were monitored every 3–4 months in the first two years and every six months thereafter. CT scans were performed if markers exceeded set thresholds or increased by over 20%. Results: During a median follow-up of 13.7 months, 73% of patients relapsed. Median HE4 levels were significantly higher in relapsed patients. A 10 IU/mL increase from baseline in CA125 had a sensitivity of 83% and specificity of 93%, while a 15 pmol/L increase in HE4 had a sensitivity of 74% and specificity of 92% for predicting relapse up to three months before CT scan detection. Conclusions: The study found that dynamic changes in HE4 and CA125 levels, rather than predefined cut-off values, are crucial for early relapse detection. These markers may offer a significant lead time over imaging, potentially enabling earlier intervention. Further research is needed to validate these findings.

Comparison of the diagnostic efficacy of systemic inflammatory indicators in the early diagnosis of ovarian cancer.

This study aimed to determine the diagnostic accuracy of CA125, HE4, systemic immune-inflammation index (SII), prognostic nutritional index (PNI), fibrinogen-to-albumin ratio (FAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the combination of the six inflammatory-nutritional markers for ovarian cancer (OC) to identify the best diagnostic indicator for OC early diagnosis. An extensive study was performed to establish the connection between these indicators and the pathological aspects of OC. A total of 170 individuals were included in this study, with 87 diagnosed with OC and 83 with benign ovarian tumors (BOTs). The diagnostic abilities of the variables were evaluated by calculating sensitivity, specificity, and area under the ROC curves. Through the use of DCA, we evaluated the variables' clinical value in the discrimination of ovarian masses. All markers showed significant diagnostic power for OC. CA125, HE4, SII, FAR, and MLR levels significantly increased from the BOTs group to the early-stage OC group. The advanced-stage OC group had significantly lower PNI values compared to the early-stage OC group but significantly higher levels of CA125, HE4, SII, NLR, and FAR. Moreover, the OC group with lymph node metastasis exhibited significantly higher levels of CA125, HE4, SII, NLR, PLR, and FAR, in contrast to the non-metastatic group, while PNI levels were significantly lower. Categorical factors, such as histological grade and pathological classification, showed noticeable discrepancies in CA125 and HE4 levels. NLR was significantly different among the pathological type groups. Among the six inflammatory-nutritional markers, the FAR displayed the greatest diagnostic value. In the analysis of logistic regression, it was observed that a combination marker containing all six inflammatory-nutritional markers exhibited a notably higher AUC value (0.881; 95% CI, 0.823 - 0.926) than any of the individual marker. PNI, NLR, PLR, MLR, SII, and FAR showed excellent diagnostic performance for OC. The combination of these markers demonstrated a superior diagnostic capability compared to each individual one. The systemic inflammatory indicators may be helpful to diagnose OC.

Clinical value of serum tumor markers in assessing the efficacy of neoadjuvant chemotherapy in advanced ovarian cancer: single-center prospective clinical study.

This study aimed to assess the clinical importance of various biomarkers, including NLR, CEA, CA199, CA125, CA153, and HE4, through dynamic testing to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) for individuals facing advanced ovarian cancer. This provides valuable information for tailoring treatment plans to individual patients, thereby leading to a more personalized and effective management of individuals facing ovarian cancer. The levels of NLR, CA125, CA199, CEA, CA153, and HE4 were detected before chemotherapy and after 3 courses of chemotherapy. Patients were categorized into ineffective and effective groups according to the effectiveness of NACT. To evaluate the factors influencing NACT's effectiveness in individuals facing advanced ovarian cancer, receiver operating characteristic (ROC) curves, predictive modeling, and multifactorial regression analysis were employed. In the effective group, the patients' age, maximum tumor diameter, and CEA and HE4 levels of the patients were significantly higher compared to those in the ineffective group (P <.05). Additionally, the difference in HE4 levels before and after treatment between the effective and ineffective groups was statistically significant (P<.05). Multifactorial analysis showed that age and maximum tumor diameter were independent risk factors impacting the effectiveness of NACT in individuals facing advanced ovarian cancer (P<.05). The ROC curve for predicting the effectiveness of NACT in individuals facing advanced ovarian cancer showed a sensitivity of 93.3% for NLR and a specificity of 92.3% for CA199. HE4 emerged as the most reliable predictor, demonstrating a specificity of 84.6% and a sensitivity of 75.3%. The area under the curve of the combined CA125 and HE4 assays for predicting the ineffectiveness of NACT in individuals facing advanced ovarian cancer was 0.825, showcasing a specificity of 74.2% and a sensitivity of 84.6%. The predictive capacity for the effectiveness of NACT in individuals facing advanced ovarian cancer is notably high when considering the sensitivity of NLR and the specificity of CA199. Additionally, the combination of CA125 and HE4 assays can obtain a better predictive effect, which can accurately select patients suitable for NACT, determine the appropriate timing of the interval debulking surgery (IDS) surgery, and achieve a satisfactory tumor reduction effect.

Elevated serum HE4 levels as a novel biomarker of disease severity and hepatic fibrosis in autoimmune hepatitis

BackgroundHuman epididymis protein 4 (HE4) has been identified as a biomarker for renal fibrosis. This study aimed to evaluate the role of HE4 in the diagnosis and determination of disease severity and hepatic fibrosis in autoimmune hepatitis (AIH). MethodsSerum HE4 levels were determined via electrochemiluminescence immunoassays in 60 healthy controls and 109 AIH patients (43 without liver cirrhosis and 66 with liver cirrhosis). Liver biopsy was performed on 56 of 109 enrolled patients. We conducted a 5-year follow-up survey of 53 enrolled patients. All continuous variables were reported as median (25th–75th percentile). ResultsSerum HE4 levels were significantly elevated in autoimmune hepatitis with liver cirrhosis (AIH-LC) patients compared with AIH patients and healthy controls [98.60 (74.15–139.08) vs 73.50 (59.88–82.00) vs 48.75 (43.38–52.93) pmol/L, p = 0.004]. The serum HE4 levels showed a positive correlation with the METAVIR scoring system in patients with liver biopsy (r = 0.711, p < 0.001). Serum HE4 levels were significantly elevated in Child–Pugh class C patients compared with Child–Pugh class B patients and Child–Pugh class A patients [106.50 (83.46–151.25) vs 110.00 (73.83–166.75) vs 77.03 (72.35–83.33) pmol/L, p = 0.006]. The diagnostic sensitivity and specificity of serum HE4 for evaluating liver cirrhosis were 69.7 % and 79.07 %, respectively, with a cutoff value of 82.34 pmol/L in enrolled patients. The logistic regression analysis showed that high levels of HE4 (≥82.34 pmol/L) were associated with AIH-LC (OR = 8.751, 95 % CI = 1.412–54.225, p = 0.020). The Kaplan-Meier curves demonstrated that high levels of serum HE4 (≥82.34 pmol/L) were associated with poor outcome (log-rank p = 0.037, HR = 0.372, 95 % CI = 0.146–0.946). ConclusionsSerum HE4 levels were found to be elevated in AIH-LC patients and exhibited a strong correlation with the severity of hepatic fibrosis, thus supporting their potential clinical value as a novel biomarker of disease severity and hepatic fibrosis in AIH.

Evaluation of serum CA125, HE4 and CA724 and the risk of ovarian malignancy algorithm score in the diagnosis of high-grade serous ovarian cancer

AimTo develop a new algorithm for the detection of high-grade serous ovarian cancer (HGSOC). MethodsPatients diagnosed with HGSOC, borderline ovarian tumours (BOTs) or benign ovarian masses (BOMs) were enrolled between February 2019 and December 2020. Patients with BOTs or BOMs were grouped as non-HGSOC. The cases were divided randomly into a training cohort (two-thirds of cases) and a validation cohort (one-third of cases). Logistic regression was used to find risk factors for HGSOC and to create a new algorithm in the training cohort. Receiver operating characteristic curves were used to compare the diagnostic value of tumour biomarkers. Sensitivity and specificity of tumour markers and the new algorithm were calculated in the training cohort and validation cohort. ResultsThis study found significant differences in age; BRCA1/2 mutation status; CA125, CA724 and HE4 levels; and Risk of Ovarian Malignancy Algorithm score between the two groups.Logistic regression analysis showed that CA125 and BRCA1/2 were risk factors for HGSOC. A new algorithm combining CA125 and BRCA1/2 increased the specificity of CA125 for diagnosis of HGSOC. The new algorithm had sensitivity of 81.08% and specificity of 93.10% in the training cohort. ConclusionThe new algorithm using CA125 and BRCA1/2 helped to distinguish between patients with HGSOC and patients with non-HGSOC.

HE4-based nomogram for predicting overall survival in patients with idiopathic pulmonary fibrosis: construction and validation.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease. Identifying biomarkers for early diagnosis is of great clinical importance. The epididymis protein 4 (HE4) is important in the process of inflammation and fibrosis in the epididymis. Its prognostic value in IPF, however, has not been studied. The mRNA and protein levels of HE4 were used to determine the prognostic value in different patient cohorts. In this study, prognostic nomograms were generated based on the results of the cox regression analysis. We identified the HE4 protein level increased in IPF patients, but not the HE4 gene expression. The increased expression of HE4 correlated positively with a poor prognosis for patients with IPF. The HR and 95% CI were 2.62 (1.61-4.24) (p < 0.001) in the training set. We constructed a model based on the risk-score = 0.16222182 * HE4 + 0/0.37580659/1.05003609 (for GAP index 0-3/4-5/6-8) + (-1.1183375). In both training and validation sets, high-risk patients had poor prognoses (HR: 3.49, 95%CI 2.10-5.80, p = 0.001) and higher likelihood of dying (HR: 6.00, 95%CI 2.04-17.67, p = 0.001). Analyses of calibration curves and decision curves suggest that the method is effective in predicting outcomes. Furthermore, a similar formulation was used in a protein-based model based on HE4 that also showed prognostic value when applied to IPF patients. Accordingly, HE4 is an independent poor prognosis factor, and it has the potential to predict IPF patient survival.

Human epididymis protein 4: Analysis of national health and nutrition examination survey data

BackgroundHuman epididymis protein 4 (HE4) is a tumor marker overexpressed in ovarian cancer and is commonly utilized to aid with diagnosis of an adnexal mass. HE4 levels vary based on pregnancy, age, menopausal status, and tobacco use. Objective(s)The objective of this study was to evaluate population-based data to examine factors that affect HE4 among adult women in the United States and stratify levels of HE4 by demographic and gynecologic factors. Study designA retrospective analysis was conducted using data from 2,480 women aged 20 + who participated in the National Health and Nutrition Examination Survey (2001–2002). From these cross-sectional data, serum HE4 and cotinine, a marker of tobacco exposure, were combined with demographic and interview data. Estimated glomerular filtration rates (eGFR) were based on serum creatinine, age, sex, and race. Other variables of interest included menopausal status, pregnancy, and various gynecologic factors. Summary HE4 data are provided as geometric means with associated 95 % confidence intervals. ResultsHE4 levels were independently associated with age, renal function, and nicotine use, all p < 0.001. Pre-menopausal women with a history of endometriosis were found to have elevated HE4 levels compared to those without, p < 0.01; however, we found no such difference among post-menopausal women. Adjusting for age, no differences in HE4 were found based on race/ethnicity, p = 0.29. HE4 levels showed statistically significant associations with income level; however, these were small and clinically irrelevant. ConclusionThis study provides evaluation of HE4 levels among a data set representative of 98.5 million non-institutionalized women in the United States and gives insight into extraneous factors that may influence these levels.

Preoperative serum level of CA153 and a new model to predict the sub-optimal primary debulking surgery in patients with advanced epithelial ovarian cancer

ObjectiveThe aim of this study was to establish a preoperative model to predict the outcome of primary debulking surgery (PDS) for advanced ovarian cancer (AOC) patients by combing Suidan predictive model with HE4, CA125, CA153 and ROMA index.Methods76 AOC Patients in revised 2014 International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent PDS between 2017 and 2019 from Yunnan Cancer Hospital were included. Clinical data including the levels of preoperative serum HE4, CA125, CA153 and mid-lower abdominal CT-enhanced scan results were collected. The logistics regression analysis was performed to find factors associated with sub-optimal debulking surgery (SDS). The receiver operating characteristic curve was used to evaluate the predictive performances of selected variables in the outcome of primary debulking surgery. The predictive index value (PIV) model was constructed to predict the outcome of SDS.ResultsOptimal surgical cytoreduction was achieved in 61.84% (47/76) patients. The value for CA125, HE4, CA153, ROMA index and Suidan score was lower in optimal debulking surgery (ODS) group than SDS group. Based on the Youden index, which is widely used for evaluating the performance of predictive models, the best cutoff point for the preoperative serum HE4, CA125, CA153, ROMA index and Suidan score to distinguish SDS were 431.55 pmol/l, 2277 KU/L, 57.19 KU/L, 97.525% and 2.5, respectively. Patients with PIV≥5 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing SDS were 73.7%, 82.9%, 62.9% and 72.3%, respectively. In the constructed model, the AUC of the SDS prediction was 0.770 (95% confidence interval: 0.654-0.887), P<0.001.ConclusionPreoperative serum CA153 level is an important non-invasive predictor of primary SDS in advanced AOC, which has not been reported before. The constructed PIV model based on Suidan's predictive model plus HE4, CA125, CA153 and ROMA index can noninvasively predict SDS in AOC patients, the accuracy of this prediction model still needs to be validated in future studies.

Multitask prediction models for serous ovarian cancer by preoperative CT image assessments based on radiomics.

High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among female reproductive system tumors. Accurate preoperative assessment is crucial for treatment planning. This study aims to develop multitask prediction models for HGSOC using radiomics analysis based on preoperative CT images. This study enrolled 112 patients diagnosed with HGSOC. Laboratory findings, including serum levels of CA125, HE-4, and NLR, were collected. Radiomic features were extracted from manually delineated ROI on CT images by two radiologists. Classification models were developed using selected optimal feature sets to predict R0 resection, lymph node invasion, and distant metastasis status. Model evaluation was conducted by quantifying receiver operating curves (ROC), calculating the area under the curve (AUC), De Long's test. The radiomics models applied to CT images demonstrated superior performance in the testing set compared to the clinical models. The area under the curve (AUC) values for the combined model in predicting R0 resection were 0.913 and 0.881 in the training and testing datasets, respectively. De Long's test indicated significant differences between the combined and clinical models in the testing set (p = 0.003). For predicting lymph node invasion, the AUCs of the combined model were 0.868 and 0.800 in the training and testing datasets, respectively. The results also revealed significant differences between the combined and clinical models in the testing set (p = 0.002). The combined model for predicting distant metastasis achieved AUCs of 0.872 and 0.796 in the training and test datasets, respectively. The combined model displayed excellent agreement between observed and predicted results in predicting R0 resection, while the radiomics model demonstrated better calibration than both the clinical model and combined model in predicting lymph node invasion and distant metastasis. The decision curve analysis (DCA) for predicting R0 resection favored the combined model over both the clinical and radiomics models, whereas for predicting lymph node invasion and distant metastasis, DCA favored the radiomics model over both the clinical model and combined model. The identified radiomics signature holds potential value in preoperatively evaluating the R0, lymph node invasion and distant metastasis in patients with HGSC. The radiomics nomogram demonstrated the incremental value of clinical predictors for surgical outcome and metastasis estimation.

Exosomal biomarkers in the differential diagnosis of ovarian tumors: the emerging roles of CA125, HE4, and C5a

ObjectiveInvestigating the utility of serum exosomal markers CA125, HE4, and C5a, both individually and in combination, for distinguishing between benign and malignant ovarian tumors.MethodsIn this study, we selected a total of 234 patients diagnosed with ovarian tumors, including 34 with malignant tumors, 10 with borderline ovarian tumors, and 190 with benign tumors. This study conducted comparisons of exosomal levels of CA125, HE4, and C5a among distinct groups, as well as making comparisons between serum and exosomal levels of CA125 and HE4. Furthermore, the diagnostic performance was assessed through Receiver Operating Characteristic (ROC) curve analysis. The Area Under the Curve (AUC) was computed, and a comparative evaluation of sensitivity and specificity was conducted to ascertain their effectiveness in determining the nature of ovarian tumors across different markers.ResultsSerum CA125 and HE4 levels, the ROMA index, exosomal CA125, HE4, C5a levels, and their combined applied value (OCS value) were notably elevated in the ovarian non-benign tumor group compared to the benign tumor group, with statistical significance (P < 0.05). Exosomal and serum levels of CA125 and HE4 exhibited a positive correlation, with concentrations of these markers in serum surpassing those in exosomes. The combined OCS (AUC = 0.871) for CA125, HE4, and C5a in exosomes demonstrated superior sensitivity (0.773) and specificity (0.932) compared to serum tumor markers (CA125, HE4) and the ROMA index. The tumor stage represents an autonomous risk factor influencing the prognosis of individuals with ovarian malignancies.ConclusionThe stage of ovarian malignancy is an independent risk factor for its prognosis. The combination of exosomal CA125, HE4 and C5a has a higher clinical value for the identification of the nature of ovarian tumours.

Effect of 3D laparoscopy versus traditional laparotomy on serum tumor markers and coagulation function in patients with early-stage endometrial cancer

ObjectivesTo investigate the impact of Three-Dimensional (3D) laparoscopy compared to traditional laparotomy on serum tumor markers and coagulation function in patients diagnosed with early-stage Endometrial Cancer (EC). MethodThe authors retrospectively analyzed the clinical data of 75 patients diagnosed with early-stage EC and categorized them into two groups based on the surgical techniques employed. The 3D group consisted of 36 patients who underwent 3D laparoscopic surgery, while the Laparotomy group comprised 39 patients who underwent traditional laparotomy. The authors then compared the alterations in serum tumor markers and coagulation function between the two groups. ResultsPostoperatively, serum levels of CA125, CA199, and HE4 were notably reduced in both groups on the third day, with the levels being more diminished in the 3D group than in the Laparotomy Group (p < 0.05). Conversely, FIB levels escalated significantly in both groups on the third-day post-surgery, with a more pronounced increase in the 3D group. Additionally, PT and APTT durations were reduced and were more so in the 3D group than in the laparotomy group (p < 0.05). ConclusionsWhen juxtaposed with traditional laparotomy, 3D laparoscopic surgery for early-stage EC appears to be more efficacious, characterized by reduced complications, and expedited recovery. It can effectively mitigate serum tumor marker levels, attenuate the inflammatory response and damage to immune function, foster urinary function recovery, and enhance the quality of life. However, it exerts a more significant influence on the patient's coagulation parameters, necessitating meticulous prevention and treatment strategies for thromboembolic events in clinical settings.

Prediction model of adnexal masses with complex ultrasound morphology.

Based on the ovarian-adnexal reporting and data system (O-RADS), we constructed a nomogram model to predict the malignancy potential of adnexal masses with sophisticated ultrasound morphology. In a multicenter retrospective study, a total of 430 subjects with masses were collected in the adnexal region through an electronic medical record system at the Fourth Hospital of Harbin Medical University during the period of January 2019-April 2023. A total of 157 subjects were included in the exception validation cohort from Harbin Medical University Tumor Hospital. The pathological tumor findings were invoked as the gold standard to classify the subjects into benign and malignant groups. All patients were randomly allocated to the validation set and training set in a ratio of 7:3. A stepwise regression analysis was utilized for filtering variables. Logistic regression was conducted to construct a nomogram prediction model, which was further validated in the training set. The forest plot, C-index, calibration curve, and clinical decision curve were utilized to verify the model and assess its accuracy and validity, which were further compared with existing adnexal lesion models (O-RADS US) and assessments of different types of neoplasia in the adnexa (ADNEX). Four predictors as independent risk factors for malignancy were followed in the preparation of the diagnostic model: O-RADS classification, HE4 level, acoustic shadow, and protrusion blood flow score (all p < 0.05). The model showed moderate predictive power in the training set with a C-index of 0.959 (95%CI: 0.940-0.977), 0.929 (95%CI: 0.884-0.974) in the validation set, and 0.892 (95%CI: 0.843-0.940) in the external validation set. It showed that the predicted consequences of the nomogram agreed well with the actual results of the calibration curve, and the novel nomogram was clinically beneficial in decision curve analysis. The risk of the nomogram of adnexal masses with complex ultrasound morphology contained four characteristics that showed a suitable predictive ability and provided better risk stratification. Its diagnostic performance significantly exceeded that of the ADNEX model and O-RADS US, and its screening performance was essentially equivalent to that of the ADNEX model and O-RADS US classification.

Serum human epididymis protein 4 is associated with disease severity in patients with IgA nephropathy

BackgroundHuman epididymis protein 4 (HE4) is a promising tumor biomarker primarily utilized for the detection of ovarian cancer. However, its potential as a novel diagnostic indicator for immunoglobulin A nephropathy (IgAN) remains unknown. The objective of this study was to investigate the feasibility of serum HE4 as a novel biomarker for patients with IgAN. MethodsThis study enrolled a total of 89 hospitalized patients with IgAN at Peking University Shenzhen Hospital between July 2020 and December 2022, along with 60 healthy control subjects matched for sex and age without evidence of comorbidities. Serum HE4 levels were measured using the Abbott Alinity automated immune analyzer, and the correlation between serum HE4 levels and biochemical markers of renal damage as well as clinicopathologic features in IgAN patients were analyzed. ResultsIn this study, serum HE4 levels were significantly elevated in patients with IgAN compared to healthy controls (116.43 ± 103.61 pmol/L vs. 35.57 ± 9.33 pmol/L, p < 0.001). There was a positive correlation between serum HE4 levels and blood urea nitrogen (r = 0.58, p < 0.001), creatinine (r = 0.73, p < 0.001), cystatin C (r = 0.82, p < 0.001), β2-microglobulin (r = 0.77, p < 0.001), α1-microglobulin (r = 0.75, p < 0.001), and glomerulosclerosis ratio (r = 0.56, p < 0.001). Conversely, a negative correlation was observed between serum HE4 levels and hemoglobin (r = -0.42, p < 0.001), albumin (r = -0.44, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = -0.83, p < 0.001). In HE4+ IgAN patients, a higher glomerulosclerosis ratio (p < 0.01) and lower eGFR levels (p < 0.001) were observed compared to HE4- patients. Furthermore, patients with higher pathological classification grade also had higher serum HE4 levels. ConclusionsSerum HE4 levels were significantly associated with both renal function and the pathological classification of patients with IgAN, indicating that HE4 may serve as a promising biomarker for assessing the severity of IgAN.

Diagnostic value of CA125, HE4, and systemic immune-inflammation index in the preoperative investigation of ovarian masses.

This study aimed to ascertain the diagnostic accuracy of CA125, HE4, systemic immune-inflammation index (SII), fibrinogen-to-albumin ratio (FAR), prognostic nutritional index (PNI), and their combination for ovarian cancer (OC) to discover an optimal combined diagnostic index for early diagnosis of OC. A thorough investigation was conducted to ascertain the correlation between these markers and the pathological characteristics of OC, thereby providing a foundation for early identification and treatment of this disorder. One hundred seventy patients with documented OC and benign ovarian tumors (BOTs) treated at Hebei General Hospital between January 2019 and December 2022 were included in this retrospective study. Data analysis was conducted using IBM SPSS Statistics version V26.0, MedCalc Statistical Software version 19.4.0, and the R Environment for Statistical Computing software (R Foundation for Statistical Computing). Isolated CA125 showed the best application value for differentiating benign ovarian tumors from OC when the defined variables were compared separately. The combination of CA125, HE4, FAR, SII, and PNI displayed a greater area under the operating characteristic curve curve than any one of them or other combinations of the 5 variables. Compared to CA125 alone, the combination of CA125, HE4, FAR, SII, and PNI showed a slight gain in sensitivity (83.91%), negative predictive value (83.91%), accuracy (85.88%), and a decrease in negative likelihood ratio (0.180%). Higher preoperative CA125, HE4, SII, and FAR levels, and lower PNI levels predicted a higher probability of advanced OC progression and lymph node metastasis. FAR has better application value than other inflammation-related markers (PNI and SII). This study suggests that preoperative serum SII, PNI, and FAR may be clinically valuable markers in patients with OC. FAR has better application value than other inflammation-related markers (PNI and SII). As we delve deeper into the inflammatory mechanisms associated with tumors, we may discover more effective combinations of tumor and inflammatory biomarkers.

Utility of human epididymis protein 4 in the differential diagnosis of ascites

Background and aimsHuman epididymal protein 4 (HE4) may be a useful tool in the differential diagnosis of malignant ascites. The aim of this study was to evaluate the diagnostic utility of HE4 for detecting malignant ascites, taking into account the possible false positives identified with adenosine deaminase (ADA), C-reactive protein (CRP), % polynuclear cells (%PMN) and glomerular filtration rate (eGFR). MethodsConcentrations of HE4, ADA, %PMN and CRP were determined in 114 samples of peritoneal fluid and creatinine in serum in order to calculate eGFR. ResultsConcentrations of HE4 presented significant differences (P = 0.028) in benign [median (interquartile range)] [582(372)] pmol/L) and malignant ascites ([8241(367)] pmol/L. Sensitivity was 21.2% and specificity 100%. Significant differences were also observed for HE4 between tumors of gynecological origin ([3165(8769)] pmol/L) and others ([665(663)] pmol/L), with a sensitivity of 67% and a specificity of 100%.Classifying according to possible false positives (ADA > 45U/L, CRP > 50 mg/L, %PMN > 90 and eGFR < 30 mL/min/1.73 m2) at maximum specificity, a sensitivity of 33.3% was obtained for HE4, with a cut-off point of 2660 pmol/L. Without possible false positives (ADA < 45U/L, CRP < 50 mg/L, %PMN < 90 and eGFR ≥ 30 mL/min/1.73 m2), a sensitivity of 37.7% was obtained at 100% specificity for a cut-off point of 1041 pmol/L. Applying these criteria to the entire group, a sensitivity of 36.4% was obtained at maximum specificity. ConclusionsHE4 allows the identification of malignant ascites with moderate sensitivity at maximum specificity. HE4 levels can differentiate between tumors of gynecological origin and others. Classification according to possible false positives increases sensitivity without losing specificity.

68Ga]Ga-FAPI-04 PET/CT in the evaluation of epithelial ovarian cancer: comparison with [18F]F-FDG PET/CT.

To compare the efficacy of [68Ga]Ga-FAPI-04 PET/CT in primary or recurrent tumors and metastatic lesions of epithelial ovarian cancer (EOC) with that of fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET/CT. Forty-nine patients (median age, 57 years; IQR, 51-66 years) with histologically proven primary or relapsed EOC were enrolled. Participants underwent [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT. The detection rate, diagnostic accuracy, semiquantitative parameters, tumor staging, and clinical management of the tracers were compared. The diagnostic performance of [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT was evaluated and compared using surgical pathology. Differences between methods regarding the peritoneal cancer index (PCI) using preoperative imaging, surgical PCI, and tumor markers (CA125, HE4) were also assessed regarding peritoneal metastases. Among the 49 patients, 28 had primary EOC; 21 had relapsed EOC. [68Ga]Ga-FAPI-04 PET/CT outperformed [18F]F-FDG PET/CT in detecting peritoneal metastases (96.8% vs. 83.0%; p < 0.001), retroperitoneal (99.5% vs. 91.4%; p < 0.001), and supradiaphragmatic lymph node metastases (100% vs. 80.4%; p < 0.001). Compared with [18F]F-FDG, [68Ga]Ga-FAPI-04 showed higher SUVmax for peritoneal metastases (17.31 vs. 13.68; p = 0.026) and retroperitoneal (8.72 vs. 6.56; p < 0.001) and supradiaphragmatic lymph node metastases (6.39 vs. 4.20; p < 0.001). Moreover, [68Ga]Ga-FAPI-04 PET/CT showed higher sensitivity compared with [18F]F-FDG PET/CT for detecting metastatic lymph nodes (80.6% vs. 61.3%; p = 0.031) and peritoneal metastases (97.5% vs. 75.9%; p < 0.001), using surgical pathology as the gold standard. Compared with [18F]F-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT led to an upgrade in 14.3% and 33.3% of treatment-naive and relapse participants, resulting in management changes in 10.7% and 19.0% of the patients, respectively. The median PCIFAPI scores were significantly higher than PCIFDG (15 vs. 11; p < 0.001) and positively correlated with CA125 and HE4 levels and surgical PCI. [68Ga]Ga-FAPI-04 PET/CT achieved higher sensitivity than [18F]F-FDG PET/CT in the detection and diagnosis of lymph node and peritoneal metastases, suggesting advantages regarding the preoperative staging of patients with EOC and, thereby, improving treatment decision-making. NCT05034146. Registered February 23, 2021.

Retracted: Clinical Efficacy of Yiqi Yangyin Decoction Combined with Docetaxel on Advanced Ovarian Cancer and the Effect on the Levels of Serum Markers VEGF, HE4, and CA125.

[This retracts the article DOI: 10.1155/2022/8401202.].

The value of serum HE4 and CA125 levels for monitoring the recurrence and risk stratification of endometrial endometrioid carcinoma

To evaluate the role of serum human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) levels for predicting and monitoring the recurrence of endometrial endometrioid carcinoma (EEC) and assessing preoperative risk stratification in EEC patients. A total of 434 EEC patients were selected for this retrospective study between May 2011 and August 2018. Serum HE4 and CA125 levels were analyzed before the initial treatment, at the first postoperative follow-up, and at recurrence or the last follow-up. Patients were risk stratified according to the European Society for Medical Oncology (ESMO), European Society for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guideline. We compared the ability of these biomarkers for prediction and monitoring by performing receiver operating characteristic curve analysis and identified optimal cut-off values by determining the Youden index. Kaplan-Meier analyses were also performed to determine prognostic value. Preoperative serum HE4 was identified as a significant predictor for the recurrence of EEC (p = 0.014). Preoperative serum HE4 and CA125 levels were related to depth of myometrial invasion, lymph node status and FIGO stage. Serum HE4 and CA125 levels were both statistically significant markers for monitoring the recurrence of EEC (P = 0.000 for each biomarker). When combined, the two markers showed higher levels of sensitivity and specificity. The two biomarkers were also significant biomarkers for evaluating the risk stratification of patients undergoing lymphadenectomy (P = 0.000 for each biomarker). For premenopausal stage I patients, preoperative serum HE4 and CA125 levels were significant predictors of the need for ovarian preservation (P = 0.000 and P = 0.002, respectively). For premenopausal patients with stage I intramucosal differentiation, preoperative serum levels of HE4 were significant predictors for fertility preservation (P = 0.024). Preoperative serum HE4 level can be used to predict the recurrence of EEC. Postoperative serum HE4 and CA125 levels can be used to monitor the recurrence of EEC and are more sensitive when combined. Preoperative serum levels of CA125 and HE4 levels are of significant value for risk stratification in EEC patients.

Association between serum HE4 and poor periodontal health in adult women

ObjectivesThe aim of this study is to explore the association between serum human epididymal protein (HE4) levels and poor periodontal health.Materials and methodsData used in our study from the National Health and Nutrition Examination Survey (NHANES) 2001–2002 and Gene Expression Omnibus database (GSE10334 and GSE16134). Periodontitis category was defined by the 2017 classification scheme based on clinical periodontal parameters. Univariate and multivariate logistic regression analyses were used to explore the relationship between serum HE4 levels and the risk of periodontitis. GSEA analysis was performed to investigate the function of HE4.ResultsA total of 1715 adult women over the age of 30 were included in our study. Compared with the lowest tertile, individuals in the highest tertile of HE4 levels were more likely to be Stage III/IV periodontitis (ORtertile3vs1 = 2.35, 95% CI: 1.35–4.21). The association was still significant in populations who were less than 60 years old, non-Hispanic white, high school graduate, 1.3 < PI ≤ 3.5, non-smoker, current smoker, non-obese, obese, and who had not diabetes mellitus or had not hypertension. In addition, HE4 expression was upregulated in diseased gingival tissues and involved in cell proliferation and immunity.ConclusionsSerum HE4 is positively associated with poor periodontal health in adult women.Clinical relevancePatients with high serum HE4 levels are more likely to have Stage III/IV periodontitis. HE4 has the potential to be used as a biomarker to predict the severity of periodontitis.

Comparison of Interleukin-6 with Other Markers in Diagnosis of Ovarian Cancer.

The lack of specific symptoms in ovarian cancer delays onset of the diagnostic process. Hence, most cases are recognized in late stages of the disease. The aim of this study was to confirm the role of Il-6 compared to other markers in diagnosis and survival in ovarian cancer. The database was collected from 13 January 2021 to 15 February 2023. In total, 101 patients with pelvic tumors with a mean age of 57.86 ± 16.39 participated in the study. In every case, CA125, HE4, CEA, CA19-9, Il-6, C-reactive protein and procalcitonin measurements were taken. Patients with ovarian borderline tumor and metastatic ovarian tumors were excluded from further analysis. Statistically significant correlations were found between diagnosis of ovarian cancer and levels of CA125, HE4, CRP, PCT and Il-6. Comparison of Il-6 with other markers revealed that longer overall survival correlated with lower values of Il-6. In the case of a higher concentration of Il-6, OS and PFS were shorter. Sensitivity and specificity of Il-6 in diagnosis of ovarian cancer were 46.8% and 77.8%, respectively, while for CA125, CRP and PCT were 76.6% and 63%; 68% and 57.5%; 36% and 77%, respectively. More investigations are needed to identify the most specific and sensitive marker for ovarian cancer.