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Int. J. Mol. Sci. 2015, 16(2), 2956-2970;

Expression and Diagnostic Value of HE4 in Pancreatic Adenocarcinoma

Department of Clinical Oncology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China
Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA
Curtis and Elizabeth Anderson Cancer Institute, Department of Surgery, Memorial Health University Medical Center, Savannah, GA 31404, USA
Department of Clinical Laboratory, Shanghai YangSi Hospital, Shanghai 200135, China
Department of Biological Sciences, Savannah State University, Savannah, GA 31404, USA
Department of Surgery & Surgical Oncology, Mount Sinai Beth Israel Medical Center, New York, NY 10003, USA
Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China
Department of Obstetrics and Gynecology, Memorial Health University Medical Center, Savannah, GA 31404, USA
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 1 December 2014 / Revised: 24 December 2014 / Accepted: 12 January 2015 / Published: 29 January 2015
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Human epididymis protein 4 (HE4) is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. The diagnostic value of HE4 in pancreatic adenocarcinoma remains unknown. Here we elucidate mRNA, protein and serum level of HE4 in pancreatic adenocarcinoma. HE4 mRNA level in tumor adjacent tissues and pancreatic adenocarcinoma tissues were tested by real time-PCR. Tissue microarray containing normal, adenocarcinoma, and adjacent pancreatic tissue was tested by immunohistochemistry (IHC). Serum level of HE4, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3) and carbohydrate antigen 125 (CA125) were detected by ELISA assay in control and tumor patients. Further we compared the sensitivity and specificity of determining HE4, CA19-9, CA15-3, and CA125 for diagnosis of pancreatic adenocarcinoma and assessed the complementary diagnostic value of HE4, CA19-9, CA15-3 and CA125. Real time PCR showed significantly increased HE4 mRNA level in pancreatic adenocarcinoma compared with control. Result of IHC showed that HE4 significantly higher expressed in the human pancreatic carcinoma tissues than in both normal and adjacent non-tumorous pancreatic tissues, and the staining intensity is inversely correlated with the clinical stage. HE4 was highly expressed in early stage of pancreatic adenocarcinoma. Serum HE4 level is higher in cases with pancreatic adenocarcinoma than in the controls. Serum HE4 levels could research to a sensitivity of 45.83% and specificity of 93.75% when the Cutoff was set at 4.59 ng/mL. The Combined HE4 and CA19-9 increased the sensitivity to 83.33%; and interestingly, the combination of HE4 with CA15-3 led to the most powerful sensitivity of 87.5%. Combined with CA19-9 and CA15-3, HE4 could be a potential biomarker to improve the diagnostic power for pancreatic adenocarcinoma. View Full-Text
Keywords: HE4; pancreatic adenocarcinoma; biomarker; serum HE4; pancreatic adenocarcinoma; biomarker; serum

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Huang, T.; Jiang, S.-W.; Qin, L.; Senkowski, C.; Lyle, C.; Terry, K.; Brower, S.; Chen, H.; Glasgow, W.; Wei, Y.; Li, J. Expression and Diagnostic Value of HE4 in Pancreatic Adenocarcinoma. Int. J. Mol. Sci. 2015, 16, 2956-2970.

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