title: Serum level of HE4 is closely associated with pulmonary adenocarcinoma progression.
abstract: The human epididymis 4 (HE4) protein is expressed in the epididymis and respiratory tract. We previously reported that HE4 is also expressed in pulmonary adenocarcinoma. The purpose of this study was to investigate serum levels of HE4 as a biological marker in pulmonary adenocarcinoma. As the trained set, 102 patients with pulmonary adenocarcinoma who underwent surgery in our institute from 2008 to 2011 were evaluated. They were compared with 58 healthy controls and 16 cases of benign lung disease. In the validation, we used 104 patients with pulmonary adenocarcinoma operated on between 2000 and 2007. Postoperative changes of serum HE4 levels were investigated in 35 patients. The level of HE4 was determined by enzyme immunometric assay and compared with clinicopathological factors. In the trained set, HE4 levels in sera in pulmonary adenocarcinoma were significantly higher than in healthy controls and benign lung disease. Receiver operating characteristic curve showed that HE4 was a good discriminator of pulmonary adenocarcinoma (cut-off point, 50.3 pM; area under curve, 0.825; 95 % confidence interval, 0.76-0.89, p < 0.001). In the validation set, serum HE4 levels were significantly correlated with age, nodal status, and carcinoembryonic antigen. Furthermore, postoperative increase of HE4 serum levels showed a significant correlation with recurrence (p = 0.032). The 5-year overall survival rate was 52.6 % in the HE4-positive group compared with 97.1 % in the HE4-negative group (p = 0.001). These data showed that HE4 expression in sera is associated with progression of pulmonary adenocarcinoma and a possible biomarker.
authors.affiliation: Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonanku, Fukuoka 814-0180, Japan. yamashi1@med.oita-u.ac.jp
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Keita
authors.initials: K
authors.lastname: Tokuishi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Moroga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ohbo
authors.forename: So
authors.initials: S
authors.lastname: Miyahara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Jun
authors.initials: J
authors.lastname: Yanagisawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hamatake
authors.forename: Masafumi
authors.initials: M
authors.lastname: Hiratsuka
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Yoshinaga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Akinori
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Kawahara
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D012372:ROC Curve; D015996:Survival Rate; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human