WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor.
There are urgent needs to develop methods for early detection of nonsmall cell lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here, we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor gene) protein that was overexpressed in the majority of NSCLC. Enzyme-linked immuno-sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients and 70 healthy individuals and that WT1 Ab titers were significantly higher in NSCLC patients compared with healthy individuals. When the cut-off level of WT1 Ab titers were fixed at mean + 3SD of those in healthy individuals, 26.4% of NSCLC patients had WT1 Ab titers over the cut-off level, and positive rates of WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%, respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage III, but not changed in stage II. Western blot analysis showed that dominant subclass of WT1 Ab was Th1-type IgG2. Interestingly, elevation of WT1 Ab titers was significantly associated with longer disease-free survival in patients with stages I-III NSCLC. These results showed that WT1 Ab could be a useful marker for early detection of NSCLC and its prognostic prediction. These results also suggested that WT1-specific immune responses played an important role in anti-cancer immunity in NSCLC.
Oji
Yusuke
Y
Department of Biomedical Informatics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kitamura
Yayoi
Y
Kamino
Eriko
E
Kitano
Aiko
A
Sawabata
Noriyoshi
N
Inoue
Masayoshi
M
Mori
Masahide
M
Nakatsuka
Shin-ichi
S
Sakaguchi
Nao
N
Miyazaki
Kaori
K
Nakamura
Michiyo
M
Fukuda
Ikuyo
I
Nakamura
Junya
J
Tatsumi
Naoya
N
Takakuwa
Tetsuya
T
Nishida
Sumiyuki
S
Shirakata
Toshiaki
T
Hosen
Naoki
N
Tsuboi
Akihiro
A
Nezu
Riichiro
R
Maeda
Hajime
H
Oka
Yoshihiro
Y
Kawase
Ichiro
I
Aozasa
Katsuyuki
K
Okumura
Meinoshin
M
Miyoshi
Shinichiro
S
Sugiyama
Haruo
H
D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000276:immunology; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000276:immunology; D011379:Prognosis; D025721:WT1 Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D025721:WT1 Proteins