Tumor Biology

, Volume 33, Issue 1, pp 103–109 | Cite as

Splice variant HE4-V3 expression is associated with favorable prognosis in pulmonary adenocarcinoma

  • Keita Tokuishi
  • Shin-ichi Yamashita
  • Kazuyuki Ohbo
  • Katsunobu Kawahara
Research Article


The human epididymis 4 (HE4) gene product, also known as whey-acidic-protein four-disulfide core domain protein 2, was identified as the transcript expressed in the epididymis and respiratory tract. HE4 is also expressed in lung adenocarcinoma. We investigated mRNA expressions of full-length HE4 and splice variants in lung adenocarcinoma, and the clinical impact of these genes was evaluated. One hundred and fifty-two patients with pulmonary adenocarcinoma underwent surgery in our institute from 2000 to 2008. We employed immunohistochemical analysis to determine the expression of HE4 and molecular analysis to evaluate full-length HE4 or splice variant gene expression in pulmonary adenocarcinoma. All of the 152 cases were full-length HE4 mRNA-positive; 88 of the 152 (57.9%) were HE4-V1-positive, and 140 of the 152 (92.1%) were HE4-V3-positive. Regarding the relationship between the clinicopathological characteristics of patients and these gene expressions, the histological subtype, tumor size, and vascular invasion were significantly associated with HE4-V3 expression. HE4-V3 expression was also closely correlated with the prognosis. The 5-year disease-free survival in the HE4-V3 high expression group showed a significantly favorable prognosis compared with the low expression group (p = 0.02). The 5-year overall survival rate in the HE4-V3 high expression group was significantly higher than in the HE4-V3 low expression group (p = 0.028). These data showed that high-level HE4-V3 expression is associated with a favorable prognosis in lung adenocarcinoma. Further investigation of HE4 splice variants may offer a new insight into this possibility.


Lung Adenocarcinoma HE4 WFDC2 Splice variant 



We appreciate the technical support of Ms. Yoko Miyanari from the Department of Surgery II, Oita University Faculty of Medicine.

Conflicts of interest

All authors disclose that no financial conflict of interest exists with any commercial entity or competitor whose products are featured, described, reviewed, evaluated, or compared in this study.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  • Keita Tokuishi
    • 1
  • Shin-ichi Yamashita
    • 1
  • Kazuyuki Ohbo
    • 2
  • Katsunobu Kawahara
    • 1
  1. 1.Department of Surgery II, Faculty of MedicineOita UniversityOitaJapan
  2. 2.Department of Histology and Cell BiologyAdvanced Medical Research Center, School of Medicine, Yokohama City UniversityYokohamaJapan

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