Human Epididymis Protein 4 as an Indicator of Acute Heart Failure in Patients with Chronic Kidney Disease
LABORATORY MEDICINE
Authors: Huang, Ying; Jiang, Hong; Zhu, Lihua
Abstract
Background: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Objective: To assess whether human epididymis protein 4 (HE4) can be useful in diagnosing acute heart failure (AHF) in patients with CKD. Methods: A cohort of 139 Han nationality female patients with CKD who were hospitalized at Renmin Hospital of Wuhan University, Wuhan, China from January 2015 through November 2017 were included. Results: Multivariable linear regression analysis showed that HE4 levels were significantly associated with N-terminal pro b-type natriuretic peptide (NT-proBNP) after adjustment of kidney function and other confounding factors. In the multivariate logistic regression analysis, HE4 was independently associated with AHF in patients with CKD (odds ratio, 2.120; 95% confidence interval, 1.034-4.344; P = .04). Moreover, according to the optimal cutoff value of 639.6 pmol per L, the area under the curve, sensitivity, and specificity of HE4 were 0.729, 74.2%, and 76.8%, respectively. Conclusions: During hospitalization, HE4 maybe an useful indicator for diagnosing AHF in patients with CKD.
WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells
JOURNAL OF OVARIAN RESEARCH
Authors: Chen, Yao; Wang, Suihai; Liu, Tiancai; Wu, Yingsong; Li, Ji-Liang; Li, Ming
Abstract
Background: WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. Methods: We investigated the role of estradiol (E2) on cell growth in estrogen-sensitive or estrogen-insensitive ovarian cancer cell lines. Real-time (RT)-PCR and western blotting were used to examine the expression of WFDC2 at RNA and protein levels. Growth traits of cells transfected with WFDC2-shRNA or blank control were assessed using MMT arrays. Cell apoptosis was analyzed using annexin V-FITC/PI and flow cytometry. Estrogen receptor expression was evaluated using RT-PCR and flow cytometry. Apoptosis-related proteins induced by E2 directly and indirectly were determined using an antibody array comparing cells transfected with WFDC2-shRNA or a blank control. Results: High-dose (625 ng/ml) E2 increased the expression of WFDC2 in HO8910 cells at both the mRNA and protein levels. However, E2 had no effect on WFDC2 expression in estrogen-insensitive SKOV3 cells. Of interest, knockdown of WFDC2 enabled a considerable estrogen response in SKOV3 cells in terms of proliferation, similar to estrogen-responsive HO8910 cells. This transformation of SKOV3 cells into an estrogen-responsive phenotype was accompanied by upregulation of estrogen receptor beta (ERa) and an effect on cell apoptosis under E2 treatment by regulating genes related to cell proliferation and apoptosis. Conclusions: We postulate that increased WFDC2 expression plays an important role in altering the estrogen pathway in ovarian cancer, and the identification of WFDC2 as a new player in endocrine-related cancer encourages further studies on the significance of this gene in cancer development and therapy.