title: Expression and diagnostic value of HE4 in pancreatic adenocarcinoma.
abstract: 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.
authors: Department of Clinical Oncology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China. 15829550278@163.com.
authors: Tianhe
authors: T
authors: Huang
authors: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. Jiang_S@mercer.edu.
authors: Shi-Wen
authors: SW
authors: Jiang
authors: Department of Clinical Laboratory, Shanghai YangSi Hospital, Shanghai 200135, China. qly12345@aliyun.com.
authors: Liangyi
authors: L
authors: Qin
authors: Curtis and Elizabeth Anderson Cancer Institute, Department of Surgery, Memorial Health University Medical Center, Savannah, GA 31404, USA. senkoch1@memorialhealth.com.
authors: Christopher
authors: C
authors: Senkowski
authors: Department of Biological Sciences, Savannah State University, Savannah, GA 31404, USA. clyle0408@gmail.com.
authors: Christian
authors: C
authors: Lyle
authors: Curtis and Elizabeth Anderson Cancer Institute, Department of Surgery, Memorial Health University Medical Center, Savannah, GA 31404, USA. terryka1@memorialhealth.com.
authors: Karen
authors: K
authors: Terry
authors: Department of Surgery & Surgical Oncology, Mount Sinai Beth Israel Medical Center, New York, NY 10003, USA. sbrower@chpnet.org.
authors: Steven
authors: S
authors: Brower
authors: Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China. chenhb@stu.edu.cn.
authors: Haibin
authors: H
authors: Chen
authors: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. Glasgow_wc@mercer.edu.
authors: Wayne
authors: W
authors: Glasgow
authors: Department of Clinical Oncology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China. weiyongchang8@163.com.
authors: Yongchang
authors: Y
authors: Wei
authors: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. liji1@memorialhealth.com.
authors: Jinping
authors: J
authors: Li
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism; D018394:CA-125 Antigen / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D012333:RNA, Messenger; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; C578959:carbohydrate antigen 199, human
references: Tumour Biol. 2012 Oct;33(5):1291-8
references: 22430259
references: Int J Cancer. 2015 May 1;136(9):2216-27
references: 25273947
references: Mol Biotechnol. 2012 Sep;52(1):59-67
references: 22382453
references: Cancer Res. 2014 Mar 1;74(5):1609-20
references: 24371222
references: Biochem Biophys Res Commun. 2012 Mar 9;419(2):274-80
references: 22342977
references: Sci Rep. 2014;4:5500
references: 24975515
references: J Clin Oncol. 2006 Jan 10;24(2):252-8
references: 16344318
references: Clin Cancer Res. 2014 Nov 15;20(22):5787-95
references: 25239611
references: Gynecol Oncol. 2013 Jun;129(3):467-71
references: 23500084
references: Cancer Chemother Pharmacol. 2013 Dec;72(6):1291-7
references: 24121456
references: Hepatobiliary Pancreat Dis Int. 2004 Aug;3(3):464-8
references: 15313690
references: Mod Pathol. 2006 Jun;19(6):847-53
references: 16607372
references: Ann Oncol. 2012 Oct;23 Suppl 7:vii33-40
references: 22997452
references: PLoS Med. 2008 Jun 10;5(6):e123
references: 18547137
references: Int J Mol Sci. 2013 Mar 15;14(3):6026-43
references: 23502467
references: Tumour Biol. 2015 Feb;36(2):1045-53
references: 25326813
references: Biochimie. 2014 Oct;105:91-8
references: 24998328
references: Tumour Biol. 2013 Dec;34(6):3279-92
references: 23949878
references: Pancreas. 2014 Jan;43(1):22-7
references: 24326364
references: Ann Oncol. 2011 Dec;22 Suppl 8:viii6-viii18
references: 22180403
references: Tumour Biol. 2014 Jul;35(7):6847-53
references: 25051914
references: Cancer Res. 2005 Mar 15;65(6):2162-9
references: 15781627
references: Clin Chem Lab Med. 2014 Nov;52(11):1639-48
references: 24829194
references: Yonsei Med J. 2013 May 1;54(3):643-9
references: 23549809
references: Clin Chem Lab Med. 2011 Dec;49(12):2081-8
references: 21923475
references: J Transl Med. 2014;12:289
references: 25323550
references: Gastroenterology. 2008 Feb;134(2):511-22
references: 18242217
references: Nat Med. 2013 Feb;19(2):227-31
references: 23353556
references: Recent Results Cancer Res. 2007;174:91-100
references: 17302189
references: Am J Obstet Gynecol. 2013 Aug;209(2):142.e1-6
references: 23583212
references: Tumour Biol. 2014 Jul;35(7):6969-71
references: 24740561
references: Clin Cancer Res. 2011 Feb 15;17(4):805-16
references: 21325298
references: Gynecol Oncol. 2012 Aug;126(2):186-91
references: 22525819
references: J Cancer. 2014 Sep 16;5(8):696-705
references: 25258651
references: Hum Pathol. 2013 May;44(5):734-42
references: 23084584
references: Tumour Biol. 2012 Oct;33(5):1335-9
references: 22528938
references: Cancer Res. 2000 Nov 15;60(22):6281-7
references: 11103784