Cancer-testis antigen BORIS is a novel prognostic marker for patients with esophageal cancer.
Esophageal squamous cell cancer (ESCC) is one of the most common lethal tumors in the world, and development of new diagnostic and therapeutic methods is needed. In this study, cancer-testis antigen, BORIS, was isolated by functional cDNA expression cloning using screening technique with serum IgG Abs from ESCC patients. BORIS was previously reported to show cancer-testis antigen like expression, but its immunogenicity has remained unclear in cancer patients. BORIS was considered to be an immunogenic antigen capable of inducing IgG Abs in patients with various cancers, including four of 11 ESCC patients. Immunohistochemical study showed that the BORIS protein was expressed in 28 of 50 (56%) ESCC tissues. The BORIS expression was significantly associated with lymph node metastasis in ESCC patients with pT1 disease (P = 0.036). Furthermore, the patients with BORIS-positive tumors had a poor overall survival (5-year survival rate: BORIS-negative 70.0% vs BORIS-positive 29.9%, log-rank P = 0.028) in Kaplan-Meier survival analysis and log-rank test. Multivariate Cox proportional hazard model demonstrated that BORIS expression was an independent poor prognostic factor (hazard ratio = 4.158 [95% confidence interval 1.494-11.57], P = 0.006). Downregulation of BORIS with specific siRNAs resulted in decreased cell proliferation and invasion ability of ESCC cell lines. BORIS may be a useful biomarker for prognostic diagnosis of ESCC patients and a potential target for treatment including by BORIS-specific immunotherapy and molecular target therapy.
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Koji
K
Okabayashi
Tomonobu
T
Fujita
Junichiro
J
Miyazaki
Tsutomu
T
Okada
Takashi
T
Iwata
Nobumaru
N
Hirao
Shinobu
S
Noji
Nobuo
N
Tsukamoto
Naoki
N
Goshima
Hirotoshi
H
Hasegawa
Hiroya
H
Takeuchi
Masakazu
M
Ueda
Yuko
Y
Kitagawa
Yutaka
Y
Kawakami
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C456540:CTCFL protein, human; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G