A Study Of The Relationship Between Human Epididymal Protein4(HE4) And Transitional Cell Carcinoma

Purpose:Urinary tract transitional cell carcinoma is a malignant tumor, occurred in the renalpelvis, ureter and bladder transitional epithelium, mainly in the bladder, is also a commonurinary tract tumors in male and female. At2006American Cancer Society statisticsconcluded that the incidence of bladder cancer is only lower than prostate cancer, lungcancer and rectal cancer in male malignant genitourinary tumors; and was ranked in10thplace of female malignancy. In recent years, the incidence of bladder cancer increased yearby year in China, the average annual growth rate is68.29%in the last15years. With thedeepening understanding of tumor molecular mechanism, we have found a large number oftumor markers, which can be used to judge the prognosis of bladder tumor, such as bladdertumor antigen, nuclear matrix protein, vascular endothelial growth factor, hyaluronic acidenzymes，Ki67, P53and so on. However, these studies are still in research stage, until nowthere was no effective tumor markers, which can accurately estimate the prognosis ofbladder cancer, so we need continued exploration.Human epididymis protein4also be known as HE4, WFDC2, Its cDNA was firstisolated from the epididymis epithelium distal by Kiehhoff, which encoded proteins wascomposite by four WAP-type disulfide core, has high homology with the extracellularprotease inhibitors. Transcription media WFDC family of proteins in leukocyte proteaseinhibitor, HE4has the same roots can be inferred that it also may have a role in innateimmunity. There is an inhibitory loop structure in WAP domains of the ring structure toinhibit protease function by inserting the structural areas of protease activity, HE4hassimilar domain, but still needs further study to explore if the HE4have proteinase inhibitorfunction. In various malignancies, HE4highly expressing in the ovarian cancer gene, ananalysis of HE4protein expression in ovarian tumors, proves that HE4’s sensitivity is72.9%,specificity is95%as a single tumor marker in ovarian cancer, so that it may has theopportunity to tumor diagnosis. Until now there is no research about HE4expression intransitional cell carcinoma, benign urinary diseases and healthy people. HE4is mainlydistributed in the ovarian tissue, in the lungs, upper respiratory tract, the colon mucosa,breast epithelial cells and urinary system, moderate expression in the renal distal convoluted tubule, so we detect the HE4content monitoring transitional cell carcinoma is possible in theserum. Therefore, we hope that through the detection of HE4levels in transitional cellcarcinoma, found the relationship between HE4and transitional cell carcinoma about tumorcharacteristics.Method:We selected45cases with transitional cell carcinoma,20cases with benign urinarysystem diseases,10cases healthy controls. We observe the patient’s clinical datas including:age, gender, body mass index and tumor grade, stage, etc. HE4levels was contrasted beforeand after surgery in urinary tract transitional cell carcinoma. Comparison of HE4levelsbetween patients with benigh urinary system disease and patients with transitional cellcarcinoma，also between invasive transitional cell carcinoma and non-invasive cases wascarried out.The object of observation is divided into three groups: benign urinary system diseasegroup, transitional cell carcinoma group and healthy control group. All observers wereexcluded from the malignant disease of other systems or organizations. Pathologicaldiagnosis is the final diagnosis. The specimens were obtained centrifuge for10minutes in1kg centrifugal force and stored at minus80degrees celsius, until be tested. The kitpurchased from Sweden the Fujirebio Diagnostis, we detect subjects serum HE4level usingenzyme-linked immunosorbent assay in20℃-25℃environment.Result：1.The average of HE4is280.88pmol/L in transitional cell carcinoma more than benignsystem urinary diseases78.14pmol/L (P <0.01) and healthy control group79.82pmol/L(P <0.01), the difference between them was significant statistically. There was no significantdifference between healthy urinary system diseases78.13pmol/L(p>0.05) and healthycontrols79.8pmol/L (p>0.05). The average of the HE4in the non-invasive transitional cellcarcinoma group is290.08pmol/L, more than benign urinary system disease group andhealthy control group, there are significant differences between them, and this difference wasstatistically significant (p<0.05). HE4levels of postoperative bladder cancer patients is176.43pmol/L, lower than the preoperative(280.88pmol/L), the difference between them wasstatistically significant (P <0.05).2. Use74.1pmol/L as a standard value, in general factors such as age, gender did nothave different significantly(p>0.05); different clinical and pathological features, tumorlocation, have no significant difference (p>0.05), there is no obvious difference between the tumor grade and the tumor stage.3. We apply SPSS software to draw a ROC curve, we found that HE4level of the bestdiagnostic cut-off point is74.1pmol/L, in this study. HE4had a sensitivity of80.0%, and aspecificity of75.0%, when the HE4level was greater than74.1pmol/L. The area under theROC curve with a standard deviation is0.058, and the AUC of the ROC curve is0.819.Conclusion:1. There are obvious differences between malignant group and non-malignant group,HE4can be used as a screening tumor maker of transitional cell carcinoma in urinary system.2. There are obvious differences between the non-invasive transitional cell carcinoma,the benign urinary system disease and the healthy control group, HE4can be used as earlydetection of transitional cell carcinoma in urinary system.3. There are no relationship between the gender, age, tumor number, location, tumorstage and grading with HE4level in TCC.