HE4 Levels Research Articles

Ovarian Cancer Biomarkers in the COVID-19 Era.

Ovarian Cancer (OC) diagnosis is entrusted to CA125 and HE4. Since the latter has been found increased in COVID-19 patients, in this study, we aimed to evaluate the influence of SARS-CoV-2 infection on OC biomarkers. HE4 values above the cut-off were observed in 65% of OC patients and in 48% of SARS-CoV-2-positive patients (not oncologic patients), whereas CA125 values above the cut-off were observed in 71% of OC patients and in 11% of SARS-CoV-2 patients. Hence, by dividing the HE4 levels into quartiles, we can state that altered levels of HE4 in COVID-19 patients were mostly detectable in quartile I (151-300 pmol/L), while altered levels in OC patients were mostly clustered in quartile III (>600, pmol/L). In light of these observations, in order to better discriminate women with ovarian cancer versus those with COVID-19, we established a possible HE4 cut-off of 328 pmol/L by means of a ROC curve. These results demonstrate that the reliability of HE4 as a biomarker in ovarian cancer remains unchanged, despite COVID-19 interference; moreover, it is important for a proper diagnosis that whether the patient has a recent history of SARS-CoV-2 infection is determined.

Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer.

Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL- 1, 0.01-10 ng mL- 1, 10-50 ng mL- 1, and 50-500 ng mL- 1). High sensitivity, low limit of detection, and limit of quantification were obtained for each linear range with a correlation coefficient above 0.99. The application stability of CA125 and HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. Immunosensors showed high selectivity in nine different antigen mixtures. The reusability of the immunosensors has been tested up to 9 cycles. The Risk of Ovarian Malignancy Algorithm score% values were calculated using the concentration of CA125 and HE4 in the blood serum and evaluated in terms of ovarian cancer risk. For the point-of-care testing, CA125 and HE4 levels at pg mL- 1 concentration were measured in blood serum samples using the developed immunosensors and a hand-held electrochemical reader in approximately 20-30s, and high recoveries were obtained. These disposable label-free immunosensors are user-friendly and can be used in point-of-care tests for rapid and practical detection of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

Detection of serum HE4 levels contributes to the diagnosis of lung cancer.

Lung cancer (LC) is the most frequently diagnosed cancer and is the leading cause of cancer-associated death. Serum markers that exhibit high sensitivity and specificity for LC may assist in the diagnosis and prognosis of LC. The banked serum samples from 599 individuals, including 201 healthy controls, 124 patients with benign lung diseases, and 274 LC cases, were used. The serum concentrations of biomarkers were determined by electrochemiluminescence immunoassay and chemiluminescence immunoassay. The results showed that the serum human epididymis secretory protein 4 (HE4) levels in the LC group were significantly higher than in the healthy and benign lung disease groups. The serum levels of HE4, NSE, and CYFRA21-1 were significantly higher in patients with LC compared to those in the benign lung disease group. The area under the area under the curve (AUC) of HE4 for discriminating LC from healthy controls was 0.851 (95% CI, 0.818-0.884) and 0.739 (95% CI, 0.695-0.783), 0.747 (95% CI, 0.704-0.790), 0.626 (95% CI, 0.577-0.676), and 0.700 (95% CI, 0.653-0.747) for NSE, CYFRA21-1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 combined with NSE, CYFRA21-1, SCC, and proGRP for cancer diagnosis was 0.896 (95% CI, 0.868-0.923). In early LC, the AUC value of HE4 for discriminating early LC from healthy controls was 0.802 (95% CI, 0.758-0.845), 0.728 (95% CI, 0.679-0.778), 0.699 (95% CI, 0.646-0.752), 0.605 (95% CI, 0.548-0.662), and 0.685 (95% CI, 0.630-0.739) for NSE, CYFRA21-1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 with NSE, CYFRA21-1, SCC, and proGRP for early LC was 0.867 (95% CI, 0.831-0.903). Serum HE4 is a promising LC biomarker, particularly for early-stage LC. Measuring serum HE4 levels may improve the diagnostic efficiency of LC.

Serum expression of tumor marker CA242 in patients with different gynecological diseases.

The aim of this study was to investigate the serum levels of CA242 in different types of gynecological diseases and its clinical significance. A total of 1021 patients with gynecological diseases and 499 healthy female controls were included in the study. The serum CA242 levels were detected and median value, -log10P value, and positive rate were calculated. Serum CA125 and HE4 levels of patients with ovarian lesions were measured, and the predictive value for ovarian cancer was statistically analyzed. Higher serum CA242 levels were observed in patients with mature teratoma, ovarian cancer, and other gynecological tumor diseases than in healthy controls. In contrast, the CA242 levels in patients with cervical intraepithelial neoplasia, uterine polyps, or endometrial hyperplasia were comparable to that of controls. Moreover, serum CA242 expression was increased in malignant uterine and ovarian diseases compared with benign ones (P<.05). Specifically, combining CA242, CA125, and HE4 yielded a higher area under the receiver operating characteristic curve than single biomarkers (P<.05). Heterogeneous increases in tumor marker CA242 expression levels are observed in different gynecological diseases, suggesting its potential value for clinical diagnosis.

Significance of serum levels of HE4, CA72-4, and G-17 in patients with gastric cancer

Significance of serum levels of HE4, CA72-4, and G-17 in patients with gastric cancer

HE4 overexpression in mice leads to leydig cell hyperplasia and spermatogensis impairment: Pathological implications for oligospermia

Previous studies have shown that HE4 cancer biomarker promoted cancer cell proliferation and tumor growth in mouse xenograft models. Interestingly, HE4 levels are significantly increased in the seminal plasma of oligoasthenospermia patients, raising a question on HE4 role(s) in spermatogenesis. We constructed an HE4 overexpression mouse model (HE4-OE), and observed that HE4-OE male adult mice had small testes, low sperm counts, and elevated serum/testis testosterone levels. These mice exhibited disorganized seminiferous tubules and impaired spermatogenesis. HE4 overexpression concentrated in Leydig cells, and these cells had hyperplasia and increased testosterone biosynthesis. Mechanistic studies indicated that the impaired spermatogenesis was likely caused by a local and direct action of HE4 in the testis rather than by a hypothalamus/pituitary-initiated dysregulation. The new findings reveal a novel HE4 function in male reproductive system, and suggest the existence of a subtype of primary oligoasthenospermia characterized by HE4 overexpression, Leydig cell hyperplasia, and elevated testosterone levels.

CircDENND4C, a novel serum marker for epithelial ovarian cancer, acts as a tumor suppressor by downregulating miR-200b/c

Research objective To explore the diagnostic value of circ-DENN domain containing 4 C (circDENND4C) in epithelial ovarian cancer (EOC) and the corresponding mechanism. Methods We determined the expression of circDENND4C and miR-200b/c in tissues and serum specimens as well as EOC cell lines using qRT-PCR. Basic clinical data, and serum HE4 and CAl25 levels were acquired from patients’ clinical records. Expression-related correlations and the diagnostic value of serum circDENND4C in EOC were also estimated. CCK-8 and flow cytometry were performed to detect the effect of circDENND4C on cell proliferation and apoptosis. Results circDENND4C level was lowest while miR-200b/c was highest in EOC tissues, followed by benign and normal tissues. Similarly, serum circDENND4C was lowest while miR-200b/c was highest in EOC patients. Moreover, serum circDENND4C was lower in patients with benign ovarian tumors than in healthy women, while miR-200b/c expression was higher. circDENND4C was negatively associated with miR-200b/c in EOC tissues and serum specimens, and serum circDENND4C was also negatively correlated with serum HE4 and CAl25 in EOC patients. circDENND4C expression in both tissue and serum was negatively related to FIGO and TNM stage, and tumor size in EOC. Serum circDENND4C could distinguish healthy persons from patients with benign ovarian tumors and EOC, and they showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis. circDENND4C upregulation significantly suppressed EOC cell proliferation and facilitated apoptosis by downregulating miR-200b/c in vitro. Conclusions Summarily, circDENND4C acts as a tumor inhibitor by downregulating miR-200b/c in EOC and could be a possible tumor marker for EOC diagnosis. KEY MESSAGES circDENND4C expression was lowest while miR-200b/c was highest in EOC tissues or serums, followed by benign and normal tissues or serums. circDENND4C was involved in malignant progression of EOC, concretely, overexpression of circDENND4C suppressed EOC cell proliferation and stimulated apoptosis via downregulating miR-200b/c, and circDENND4C expression in both tissue and serum was closely related to FIGO and TNM stages and tumor size in EOC. Serum circDENND4C showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis. HIGHLIGHTS circDENND4C expression was lowest while miR-200b/c was highest in EOC tissues, followed by benign and normal tissues. Serum circDENND4C was lowest while miR-200b/c was highest in EOC patients, followed by benign patients and healthy women. Overexpression of circDENND4C suppresses EOC cell proliferation and stimulates apoptosis via downregulating miR-200b/c. circDENND4C expression in both tissue and serum was closely related to FIGO and TNM stage and tumor size in EOC. Serum circDENND4C showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis.

Urine CA125 and HE4 for the Detection of Ovarian Cancer in Symptomatic Women.

The symptoms of ovarian cancer are vague, and current risk assessment tools such as serum CA125 and transvaginal ultrasound scan fail to reliably detect the disease early. This study aimed to evaluate urine CA125 and HE4 as diagnostic biomarkers for ovarian cancer in symptomatic women. Paired urine and serum samples were collected from women undergoing treatment for ovarian cancer (cases) or investigations for gynaecological symptoms (controls). Biomarkers were measured using an automated chemiluminescent enzyme immunoassay analyser. Standard diagnostic accuracy metrics were calculated. In total, 114 women were included, of whom 17 (15%) were diagnosed with an epithelial ovarian malignancy. Levels of urine CA125 and HE4 were significantly elevated in women with ovarian cancer compared to controls [CA125: 8.5 U/mL (IQR: 2.4-19.5) vs. 2.3 U/mL (IQR: 1.0-6.4), p = 0.01. HE4: 12.0 nmol/L (IQR: 10.3-23.1) vs. 6.7 nmol/L (IQR: 3.4-13.6), p = 0.006]. Urine CA125 and HE4 detected ovarian cancer with an AUC of 0.69 (95% CI: 0.55-0.82) and 0.71 (95% CI: 0.69-0.82), respectively (p = 0.73). A combination of urine CA125 and HE4 at optimal thresholds had a sensitivity of 82.4% (95% CI: 56.6-96.2) and was comparable to the sensitivity of serum CA125 [88.2% (95% CI: 63.6-98.5)]. Larger studies are required to confirm our findings, standardise urine collection, and evaluate optimal biomarker thresholds. Urine CA125 and HE4 may be useful non-invasive diagnostic tools to triage women for formal ovarian cancer investigations.

Clinical characteristics and serum CA19-9 combined with HE4 are valuable in diagnosing endometriosis-associated ovarian cancer.

Endometriosis-associated ovarian cancer (EAOC) is difficult to diagnose because of its low incidence, uncertain risk factors, and the absence of effective markers. This study aimed to investigate the clinical characteristics of EAOC and identify useful serological markers. We retrospectively studied the clinical characteristics of patients with EAOC and ovarian endometriosis, obtained between January 1, 2011 and October 31, 2021. Univariate and multivariate logistic regression analyses were used to explore the relationship between clinical characteristics and EAOC. Receiver operating characteristic curves were applied to access the diagnostic value of serological markers in EAOC. In total, the clinical characteristics of 220 patients were obtained; 44 with EAOC and 176 with ovarian endometriosis. EAOC patients were older (46.20 vs. 36.26 years, P< 0.001) and had larger tumors (9.10 vs. 6.73 cm, P= 0.003) together with higher CA19-9 (21.44 vs. 4.72 U/mL, P< 0.001) and HE4 levels (62.35 vs. 44.19 pmol/L, P< 0.001) when compared with ovarian endometriosis patients. Multivariate analysis showed that HE4 greater than 59.7 pmol/L, CA19-9 greater than 8.5 U/mL, age 42 years or older, and tumor length 9.2 cm or longer were independent risk factors for EAOC. Significantly, CA19-9 combined with HE4 had high sensitivity (72.73%) and specificity (78.41%) in diagnosing EAOC. Age over 42 years, large ovarian tumor, serum CA19-9 and HE4 are valuable in the diagnosis of EAOC.

Evaluation of He4 Use in the Diagnosis of Ovarian Cancer: First and Second Recurrence, and an Analysis of HE4 Concentration during Second- and Third-Line Chemotherapy.

HE4 is a commonly used tumor marker for ovarian cancer (OC) diagnosis. In our study, we aimed to assess its use in the diagnosis of subsequent OC recurrences and to evaluate its changes during recurrence diagnosis and the subsequent lines of chemotherapy treatment. This retrospective single center study was conducted on 188 patients treated for ovarian cancer recurrence at the Department of Gynecological Surgery and Gynecological Oncology. The sensitivity and specificity of HE4 for patient survival prediction were analyzed using Receiver Operating Characteristics (ROC) and area under the curve (AUC) with 95% confidence intervals (95% CI). Survival times to reach one of the endpoints (OS, PFS, TFI, PFS2, TFI2) were analyzed using Kaplan-Meier curves. Elevated HE4 levels at the time of first relapse diagnosis, and after the third and the last course of second-line chemotherapy, significantly influences the time from OC diagnosis until first disease recurrence (PFS2) (p = 0.005, p = 0.015 and p = 0.002, respectively). Additionally, elevated serum HE4 concentration at the time of OC diagnosis (p = 0.012), and its later recurrence (first (p < 0.001), and second recurrent diagnosis (p = 0.143)) significantly influences patient OS. Increased HE4 concentration at the end of chemotherapeutic treatment negatively affects overall patient survival ((p = 0.006 for second line chemotherapy and (p = 0.022) for elevated HE4 concentration after the last course of third-line chemotherapy). Our preliminary results show an encouraging diagnostic and prognostic role of HE4 in recurrent ovarian cancer. HE4 measurements at different treatment time points during the second- and third-line chemotherapy treatment seem to correlate with patient survival.

Are ROMA and HE4 More Accurate than CA-125, in Predicting of Ovarian Epithelial Carcinoma?

Evaluation of ovarian tumors based on tumor markers could have high clinical importance. In this study, we aimed to assess the predictive value of HE4 and Risk of Ovarian Malignancy Algorithm (ROMA) compared to CA-125 in the Malignancy of ovarian epithelial masses. This cross-sectional study was performed in 2020-2021 including 203 patients. Serum HE4 and CA-125 levels were checked before surgery. According to the pathology report (benign, borderline, or malignant epithelial mass), the predictive values of the three markers were evaluated. About 146 cases were benign; 14 cases were borderline and 43 cases were malignant. Most patients (69.8%) in the malignant group were in stage 3. Significantly higher levels of all three markers (CA-125, HE4, and ROMA) were found in patients with malignant tumors compared to benign or borderline tumors (P < 0.001 for all). The sensitivity of CA-125 was the highest (90.7%) in pre- and post-menopausal patients but the specificity of HE4 and ROMA were higher than CA-125 (98.1% and 97.5%, respectively, versus 86.9% for CA-125). In post-menopausal patients, both sensitivities of HE4 and ROMA were 90.5% and the specificity and sensitivity of CA-125 were the highest (95.2% and 100%). In premenopausal patients, the sensitivity of ROMA (90.9%) and the specificity of HE4 (100%) were the highest. HE4 and ROMA are not necessary for postmenopausal patients in low-resource areas and a check of serum CA-125 will be enough. The higher-cost, ROMA, and HE4 checks are recommended in premenopausal people because they are more sensitive.

Evaluation of HE4 as a prognostic biomarker in uterine cervical cancer,

IntroductionUterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. MethodWhole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. ResultSerum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P < 0.05), stage (P < 0.16), tumor size, and parametrial invasion. Negative result was seen with vaginal invasion, lymph node involvement & cases which had recurrence. Various histological types showed variable results. So the serum level of HE4 (sHE) level may play a role in the diagnosis & therapeutic monitoring of UCC. But the prognostic evaluation needs further studies. ConclusionsHE4 is useful in the diagnosis of cervical cancer, but its prognostic significance is under the question marks. It may be associated with higher values in higher stages. Higher parity of the patient is associated with higher level of HE4 in UCC.

Changes in lung cancer-related serum tumor markers in patients with chronic kidney disease and determination of upper reference limit.

To investigate the changes in lung cancer-related serum tumor markers in patients with chronic kidney disease (CKD) and determine the upper reference limit for patients with different stages. Included inpatients diagnosed with CKD who did not receive dialysis temporarily in our hospital from March to September 2020. Changes in serum CA125, HE4, CYFRA21-1, SCCA, NSE and ProGRP in CKD patients were analyzed. The non-parametric method was used to estimate the upper reference limit of the above indicators in patients with CKD stages 2-5. The serum levels of HE4, CYFRA21-1, SCCA, and ProGRP in the CKD group were significantly higher than those in the healthy control group; CA125 and NSE levels were not statistically different. The false positives of SCC, CYFRA21-1, ProGRP, and HE4 increased significantly with the CKD stage. Still, NSE and CA125 did not show a significant increasing trend. Both HE4 and ProGRP have independent upper reference limits from CKD2 to CKD5 stage, namely 220.8 pmol/l and 101.4 pg/ml in the CKD2 stage, 496.7 pmol/l and 168.63 pg/ml in CKD3 stage, 4592.4 pmol/l and 272.8 pmol/l for CKD4 stage, CKD5 stage was 4778.2 pmol/l and 491.6 pmol/l. This study preliminarily determined the upper reference limits of Lung cancer-related tumor markers in patients with different CKD stages and provided laboratory support for the rational use and interpretation of Lung cancer-related tumor markers in special populations.

EPCAM+CD45+ cells in ascitic fluid of patients with ovarian cancer: a relationship with tumor marker levels and tumor grade

Purpose of the study: to assess the relationship between atypical/hybrid forms of EpCAM+CD45+ cells in ascitic fluid of ovarian cancer patients and the levels of cancer markers, such as CA125 and HE4, and the tumor grade. Material and methods. The study included 48 patients with newly diagnosed ovarian cancer (42 patients with stage Ic–IV ovarian cancer and 6 patients with borderline ovarian tumors (Bots). The age of the patients ranged from 36 to 76 years. the study material included ascitic fluid and blood samples. the presence of atypical/hybrid forms of EpCAM+CD45+ cells in ascitic fluid was identified by laser multicolor flow cytometry. The levels of CA125 and HE4 markers were measured by ELISA. Results. The number of EpCAM+CD45+ cells in ascitic fluid of patients with serous ovarian carcinoma was 1.02 (0.30; 2.68) cells/µl (0.55 (0.03; 4.51) cells/µl in patients with low-grade serous carcinoma (LGSC) and 1.36 (0.41; 2.68) cells/µl in patients with high-grade serous carcinoma (HGSC). The number of EpCAM+CD45+ cells in ascitic fluid of serous ovarian carcinoma was shown to have a strong correlation with СА125 and HE4 levels in blood serum (R=0.60; р&lt;0.01 and R=0.34; р=0.05, respectively). In the LGSC group, there was a strong direct correlation between the number of EpCAM+CD45+ cells in ascitic fluid and the levels of CA125 and HE4 markers in blood serum (R=0.93; p&lt;0.01 and R=0.68; p=0.03, respectively). No differences in the levels of EpCAM+CD45+ cells in ascitic fluid and CA125/ HE4 markers in blood serum between patients with HGSC and LGSC were found. the levels of atypical/hybrid forms of cells in ascitic fluid and CA125/ HE4 markers in blood serum were significantly lower in patients with Bots than in patients with serous ovarian carcinoma (p=0.02 for EpCAM+CD45+ cells and p&lt;0.01 for СА125/ HE4 levels). Conclusion. The relationship between the number of EpCAM+CD45+ cells in ascitic fluid and the levels of CA125 and HE4 markers in blood serum of patients with serous ovarian carcinoma was found. However, no differences in the levels of EpCAM+CD45+ cells in ascitic fluid and CA125/ HE4 markersin blood serum between patients with HGSC and LGSC were observed.

Measurement of HE4 six months after first-line treatment as optimal time in identifying patients at high risk of progression advanced ovarian cancer.

The objective of the study was to assess the usefulness of determining HE4 and CA125 in ovarian cancer patients, to indicate which of the measurements may be optimal in the prognosis, depending on the treatment scheme. The concentrations of CA125 and HE4 were performed in 70 patients with advanced ovarian cancer during I-line therapy and after treatment. The subjects were divided based on the treatment scheme: group I - primary surgery and adjuvant chemotherapy, II- neoadjuvant therapy, and surgery. Multivariate analysis showed that HE4 levels six months after treatment was significantly higher in patients with disease progression. ROC analysis in the group of patients treated with neoadjuvant therapy showed that the cut-off values indicating relapse for HE4 and CA125 after six months of follow up, were > 90.4 pmol/L, > 25.6 IU/mL, respectively. In the group of patients not treated with neoadjuvant therapy, the cut-off points differentiating patients with progression were: HE4 > 79.1 pmol/L, CA125 > 30.7 IU/mL. We demonstrated significantly higher HE4 and CA125 at both 6- and 12-months follow-up in patients treated with neoadjuvant therapy. In both groups of patients, the cut-off points were lower than those proposed by the manufacturer of the kits. Measurement of HE4 six months after treatment may be useful in identifying patients at high risk of progression, especially when CA125 levels may be non-specifically elevated. The cut-off values indicating relapse for HE4 and CA125 after six months of follow up may be lower than the normal range.

Development of exploratory algorithms to aid in risk of malignancy prediction of indeterminate pulmonary nodules

Early detection of lung cancer allows for earlier stage treatment initiation and improved patient prognosis. This report focuses on utilization of combining patient demographic information with non-invasive biomarkers and their potential ability to predict risk of malignancy of nodules. A pilot study cohort of 141 subjects with IPNs (105 stage I cancer and 36 benign nodules) were collected by RUMC. The demographic variables of gender, age, sex, race, ethnicity, nodule size (mm), and smoking pack years, as well as the plasma levels of CA-125, SCC, CEA, HE4, ProGRP, NSE, Cyfra 21-1, hs-CRP, Ferritin, IgG, IgG1, IgG2, IgG3, IgG4, IgE, IgM, IgA, KFLC, and LFLC, were assessed for this cohort. Multivariable analyses of the previously aforementioned biomarkers and demographic variables yielded a reduced algorithm consisting of CA-125, total IgG, IgA, IgM, IgE, LFLC, nodule size, and smoking pack years with improved performance (AUC 0.82, 95 %CI 0.74–0.90) over the same analysis of the demographic variables (age, nodule size, and smoking pack years) alone (AUC 0.70, 95 %CI 0.61–0.78). This reduced algorithm of biomarkers and demographic variables may aid in assessing the risk of IPN malignancy which could be a useful stratification tool in early detection of lung cancer in high-risk subjects.

CT imaging phenotypes linked to CA125 and HE4 biomarkers are highly predictive in discriminating between hereditary and sporadic ovarian cancer patients.

Hereditary ovarian cancers (HOC) represent about 23% of ovarian cancer (OC) cases: they are most frequently related to germline mutations in the BRCA genes. We aimed to compare CA125/HE4 serum levels and Computed Tomography (CT) features at time of ovarian cancer (OC) diagnosis in two populations: BRCA mutant and BRCA wild-type (WT) OC, and to investigate the relationship between this laboratory and radiological biomarker and BRCA mutation status. This retrospective study included 60 newly diagnosed OC patients with FIGO stage IIIC-IV disease, tested for BRCA1/2 germline mutation status of which preoperative CT scan and serum tumor marker assay were available. The median level of CA125 (708 U/mL) was significantly higher (p < 0.002) in BRCA1/2 mutated patients than in WT patients (176 U/mL), whereas the median level of HE4 (492 pmol/L) was significantly higher (p < 0.002) in WT than in BRCA-mutated patients (252 pmol/L). BRCA mutation carriers showed a higher incidence of bilateral ovarian masses (p = 0.0303) characterized by solid structures (p < 0.00001), higher peritoneal tumor load, macronodular implants >2 cm (p = 0.000099), increased frequency of lymphadenopathies (p = 0.019), and metastasis (p = 0.052) compared to patients with BRCA WT. Tumor markers and CT patterns may help in identifying BRCA mutation status in OC directing patients towards a personalized treatment.

Clinical and molecular evaluation of patients with ovarian cancer in the context of drug resistance to chemotherapy.

The present study aimed to evaluate changes in the expression patterns at the gene and protein levels associated with drug resistance. The study group included 48 women who had a histopathologically confirmed diagnosis of stage I-IV ovarian cancer, they were divided into two subgroups (groups A and B). In group A, there were 36 patients in whom surgical treatment was supplemented with first-line chemotherapy according to current standards. Within this patient group, 5 had stage I (14%), 5 had stage II (14%), 25 had stage III (69%), and 1 had stage IV ovarian cancer (3%). Drug resistance was found after the third cycle of chemotherapy in 17 patients (71%) and after the sixth cycle in 7 patients (29%). Group B included 12 women with type I ovarian cancer, including 11 with stage I and 1 patient with stage IV ovarian cancer. The oncological treatment required only surgery. The control group (C) included 50 women in whom the uterus and adnexa were surgically removed for non-oncological reasons. Significantly higher levels of carcinoma antigen 125 CA-125 and human epididymis protein 4 HE4 were observed in group A and in menopausal women. Moreover, drug resistance was associated with significantly higher levels of CA-125 (p < 0.05). The genes UBA2, GLO1, STATH, and TUFT1 were differentiated in test samples from control samples. Moreover, drug resistance was associated with significantly higher expression of GLO1. The results of these assessments indicated the strong link between UBA2 and hsa-miR-133a-3p and hsa-miR-133b; GLO1 and hsa-miR-561-5p; STATH and hsa-miR-137-3p and hsa-miR-580-3p; and TUFT1 and hsa-miR-1233-3p and hsa-miR-2052. Correlation analysis showed a significant correlation between CA-125 and HE4 levels. Moreover, a significant correlation between TUFT1 mRNA and UBA2, GLO1, STATH (negative correlation), and TUFT1 in relation to CA-125 and HE4 (p < 0.05) was noted in all patients. In view of the lack of screening tests for ovarian cancer, the occurrence of the described correlation may be inscribed as an attempt to establish an assay that meets the criteria of a screening test and thus increase the early diagnosis of ovarian cancer.

Predicting value of HE4 and CA125 markers for optimal cytoreductive surgery in ovarian cancer patients.

We conducted a cross-sectional study to evaluate the role of serum levels of CA125 and HE4 in predicting optimal cytoreductive surgery. Eligible women who had been diagnosed with ovarian cancer based on both clinical and imaging criteria were enrolled in this study. Serum levels of CA 125 and HE4 were checked before surgery and all patients underwent complete surgical staging. After completion of the pathological evaluation, data were entered in SPSS version 23. One hundred and ten individuals were enrolled in our study. We divided cases between two groups: stage I to Ш b and stage Шc to IV. Serum level of HE4 >170 pmol/L can predict optimal cytoreductive surgery before operation. (sensitivity:80% and specificity 70%) and serum level of CA 125 > 320 UI/mL can predict optimal cytoreductive surgery before operation. (sensitivity:80% and specificity 70%). Our data demonstrated a negative predictive value of about 80% for both HE4 and CA125. Based on these cut-off, unnecessary surgery can be avoided in many cases, however, it is unwise to ignore clinical performance and radiological findings. Nevertheless, we can say the evaluation of tumor markers is feasible and helpful in predicting optimal surgery.

Urine CA125 and HE4 for the Triage of Symptomatic Women with Suspected Endometrial Cancer.

Simple SummaryWomen with suspected endometrial cancer undergo investigations that can be painful and anxiety-provoking. These tests are avoidable, as only 5–10% of symptomatic women have underlying cancer. A simple and accurate urine-based test to triage symptomatic women in the community will improve patient care. In this study, we evaluated the performance of two proteins (CA125 and HE4) for the detection of endometrial cancer in urine samples of 153 symptomatic women. We discovered that both proteins were significantly elevated in the urine of women with cancer compared to those without cancer. Urine CA125 performed better than HE4 in detecting endometrial cancer. When we combined urine CA125 and endometrial thickness measurement by transvaginal ultrasound scan, there was improvement in the detection of endometrial cancer. This is the first study to evaluate the performance of these proteins in urine for endometrial cancer detection. Confirmation in a larger sample is needed. A simple, noninvasive and accurate detection tool that can triage women with suspected endometrial cancer for definitive testing will transform patient care. The aim of this study was to evaluate urine CA125 and HE4 levels for the detection of endometrial cancer in symptomatic women. This was a cross-sectional diagnostic accuracy study of 153 symptomatic women who underwent urgent diagnostic investigations for suspected endometrial cancer at a large gynecological cancer center. Urine samples were collected prior to routine clinical procedures. Urine CA125 and HE4 levels were determined using automated chemiluminescent enzyme immunoassays. Univariate and multivariable receiver operating characteristic (ROC) curve analyses were performed. Urine CA125 and HE4 were discovered to be significantly elevated in women with endometrial cancer, compared to controls (p < 0.001 and p = 0.01, respectively). Urine CA125 and HE4 detected endometrial cancer with an area under the ROC curve (AUC) of 0.89 (0.81, 0.98) and 0.69 (0.55, 0.83), respectively. CA125 exhibited good discriminatory potential for Type I and early-stage tumors (AUC 0.93 and 0.90, respectively). A diagnostic model that combined urine CA125 and transvaginal ultrasound-measured endometrial thickness predicted endometrial cancer with an AUC of 0.96 (0.91, 1.00). Urine CA125 displays potential as a diagnostic tool for symptomatic women with suspected endometrial cancer. When combined with transvaginal ultrasound-measured endometrial thickness, this patient-friendly, urine-based test could help triage women for invasive diagnostics or safe reassurance, reducing costs and improving patient experience.