Splice variant HE4-V3 expression is associated with favorable prognosis in pulmonary adenocarcinoma.
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.
Department of Surgery II, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan.
Keita
K
Tokuishi
Shin-ichi
S
Yamashita
Kazuyuki
K
Ohbo
Katsunobu
K
Kawahara
D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000235:genetics; D000081102:WAP Four-Disulfide Core Domain Protein 2
D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human