Analysis of serum level of HE4 and CA125 considering selected risk factors among patients with endometrioid endometrial cancer

Abdalla, Nabil; Piórkowski, Robert; Słomka, Anna; Kania, Małgorzata; Sawicki, Włodzimierz; Cendrowski, Krzysztof

doi:10.5114/wo.2016.65606

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…It is postulated that HE4 is better than CA125 in diagnosing patients with EOC due to high specificity. However, HE4 increases with age, smoking and renal diseases 9 . There are several methods to estimate serum CA125 and serum HE4, such as Enzyme-linked immunosorbent assay (ELISA), Radioimmunoassay (RIA), Chemiluminiscence immunoassay (CLIA) and Electrochemiluminesce immunoassay (ECLIA).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic measures comparison for ovarian malignancy risk in Epithelial ovarian cancer patients: a meta-analysis

Suri

Vanamail

Ammalli

et al. 2021

Sci Rep

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Epithelial ovarian cancer has become the most frequent cause of deaths among gynecologic malignancies. Our study elucidates the diagnostic performance of Risk of Ovarian Malignancy Algorithm (ROMA), Human epididymis secretory protein 4 (HE4) and cancer antigen (CA125). To compare the diagnostic accuracy of ROMA, HE-4 and CA125 in the early diagnosis and screening of Epithelial Ovarian Cancer. Literature search in electronic databases such as Medicine: MEDLINE (through PUBMED interface), EMBASE, Google Scholar, Science Direct and Cochrane library from January 2011 to August 2020. Studies that evaluated the diagnostic measures of ROMA, HE4 and CA125 by using Chemilumincence immunoassay or electrochemiluminescence immunoassay (CLIA or ECLIA) as index tests. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We included 32 studies in our meta-analysis. We calculated AUC by SROC, pooled estimated like sensitivity, specificity, likelihood ratio, diagnostic odds ratio (DOR), Tau square, Cochran Q through random effect analysis and meta-regression. Data was retrieved from 32 studies. The number of studies included for HE4, CA125 and ROMA tests was 25, 26 and 22 respectively. The patients with EOC were taken as cases, and women with benign ovarian mass were taken as control, which was 2233/5682, 2315/5875 and 2281/5068 respectively for the markers or algorithm. The pooled estimates of the markers or algorithm were sensitivity: ROMA (postmenopausal) (0.88, 95% CI 0.86–0.89) > ROMA (premenopausal) 0.80, 95% CI 0.78–0.83 > CA-125(0.84, 95% CI 0.82–0.85) > HE4 (0.73, 95% CI 0.71–0.75) specificity: HE4 (0.90, 95% CI 0.89–0.91) > ROMA (postmenopausal) (0.83, 95% CI 0.81–0.84) > ROMA (premenopausal) (0.80, 95% CI 0.79–0.82) > CA125 (0.73, 95%CI 0.72–0.74), Diagnostic odd’s ratio ROMA (postmenopausal) 44.04, 95% CI 31.27–62.03, ROMA (premenopausal)-18.93, 95% CI 13.04–27.48, CA-125-13.44, 95% CI 9.97–18.13, HE4-41.03, 95% CI 27.96–60.21 AUC(SE): ROMA (postmenopausal) 0.94(0.01), ROMA (premenopausal)-0.88(0.01), HE4 0.91(0.01), CA125-0.86(0.02) through bivariate random effects model considering the heterogeneity. Our study found ROMA as the best marker to differentiate EOC from benign ovarian masses with greater diagnostic accuracy as compared to HE4 and CA125 in postmenopausal women. In premenopausal women, HE4 is a promising predictor of Epithelial ovarian cancer; however, its utilisation requires further exploration. Our study elucidates the diagnostic performance of ROMA, HE4 and CA125 in EOC. ROMA is a promising diagnostic marker of Epithelial ovarian cancers in postmenopausal women, while HE4 is the best diagnostic predictor of EOC in the premenopausal group. Our study had only EOC patients as cases and those with benign ovarian masses as controls. Further, we considered the studies estimated using the markers by the same index test: CLIA or ECLIA. The good number of studies with strict inclusion criteria reduced bias because of the pooling of studies with different analytical methods, especially for HE4. We did not consider the studies published in foreign languages. Since a few studies were available for HE4 and CA125 in the premenopausal and postmenopausal group separately, data were inadequate for sub-group analysis. Further, we did not assess these markers' diagnostic efficiency stratified by the stage and type of tumour due to insufficient studies.

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Section: Introductionmentioning

confidence: 99%

Diagnostic measures comparison for ovarian malignancy risk in Epithelial ovarian cancer patients: a meta-analysis

Suri

Vanamail

Ammalli

et al. 2021

Sci Rep

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“…The same authors also reported higher HE4 protein levels in women with atypical hypertrophy of endometrium in comparison to healthy women with normal endometrium [11]. There is a similar study concerning the clinical stage, the degree of differentiation and prognosis conducted by a Polish team, which leads to the same conclusions [12]. This may be of great clinical importance, as the initial histologic grade and the tumor size have an impact on overall survival in endometrial cancer [13].…”

Section: Discussionmentioning

confidence: 73%

Usefulness of HE4 protein in differentiation of pelvic masses in woman

Brenk

Bodzek

Baliś

et al. 2019

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Introduction: HE4 protein (human epididymis protein-4), which is the fourth subfraction of human epithelial protein, is a glycoprotein widely used as a tumor marker in ovarian cancer. If was first discovered in the epididymal epithelium and recognized as a protease inhibitor contributing to sperm maturation. The plasma HE4 concentration may also be increased in gynecological pathologies other than ovarian cancer. Material and methods: The study was conducted between 2016 and 2017 among patients hospitalized in the Academic Department of Gynaecology. A total of 191 women were examined. Depending on the type of pathology which was the reason for hospitalization, 4 groups of patients were identified in the study. The first of these included 30 patients with ovarian cancer, the second 33 patients with benign ovarian lesion, the third 50 patients with endometrial cancer, and the fourth 28 patients with leiomyomas. Results: The highest concentration of HE4 protein was found in women with ovarian cancer, and it was statistically significantly higher compared to all other groups. Lower HE4 protein concentration than in women with ovarian cancer was reported in women with endometrial cancer, but it was statistically significantly higher compared to patients with uterine fibroids. Conclusions: This marker may have significant clinical value in the differentiation of benign ovarian pathology from ovarian cancer. The study confirms the validity of using HE4 results in the assessment of potential malignancy of ovarian and endometrial lesions.

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“…It was observed that HE4 expression levels in malignant tissues are positively correlated with tumor sizes and stages, invasion and metastasis, and negatively correlated with patient survival, in ovarian as well as endometrial cancers [31][32][33]. In pancreatic cancers, higher HE4 expression levels in tumor tissues are closely correlated with larger tumor sizes and more advanced stages of malignancies [24].…”

Section: Discussionmentioning

confidence: 99%

HE4 overexpression decreases pancreatic cancer Capan-1 cell sensitivity to paclitaxel via cell cycle regulation

Guo

et al. 2020

Cancer Cell Int

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Background: Paclitaxel is a first-line chemotherapy drug for pancreatic, ovarian, endometrial cancers and other malignancies. However, its efficacy is often compromised by decreased cell sensitivity or the development of resistance. Human epididymis protein 4 (HE4) is highly expressed in gynecologic and pancreatic cancer tissues, and its serum levels are used for patient triage and assistant diagnosis of gynecologic cancers. Previous studies have shown that HE4 overexpression could promote cancer cell proliferation and the growth of tumor xenografts, which suggests its potential involvement in cancer chemosensitivity. Methods: Two pancreatic cancer cell lines, Capan-1 and Suit-2, were transiently transfected with an HE4 overexpression plasmid, and transfected cells were treated with paclitaxel. S-phase cells were labeled using BrdU, and cell positivity rates were determined by counting BrdU-positive cells. Following HE4 overexpression and/or drug treatment, a western blotting analysis was performed to determine the protein alterations of PCNA and p21, two important cell cycle regulators. Results: HE4 overexpression not only promoted the proliferation of the Capan-1 pancreatic cells, but also significantly decreased cell sensitivity to paclitaxel. Results from western blotting showed that paclitaxel inhibited cell proliferation by decreasing the expression of PCNA and increasing the expression of p21. Data analysis indicated interactive actions between HE4 function and paclitaxel effects, both converging to cell cycle regulation. Conclusion: These findings suggest that HE4 could be a potential therapeutic target for the sensitization of pancreatic cancer cells to paclitaxel treatment. HE4 expression levels may be used to predict the sensitivity of pancreatic cancer patients to paclitaxel.

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Analysis of serum level of HE4 and CA125 considering selected risk factors among patients with endometrioid endometrial cancer

Cited by 6 publications

References 25 publications

Diagnostic measures comparison for ovarian malignancy risk in Epithelial ovarian cancer patients: a meta-analysis

Diagnostic measures comparison for ovarian malignancy risk in Epithelial ovarian cancer patients: a meta-analysis

Usefulness of HE4 protein in differentiation of pelvic masses in woman

HE4 overexpression decreases pancreatic cancer Capan-1 cell sensitivity to paclitaxel via cell cycle regulation

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