Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas

被引:109
作者
Ishikawa, Nobuhisa [1 ,2 ]
Takano, Atsushi [1 ]
Yasui, Wataru [3 ]
Inai, Kouki [4 ]
Nishimura, Hitoshi [5 ]
Ito, Hiroyuki [6 ]
Miyagi, Yohei [7 ]
Nakayama, Haruhiko [6 ]
Fujita, Masahiro [8 ]
Hosokawa, Masao [8 ]
Tsuchiya, Eiju [7 ]
Kohno, Nobuoki [2 ]
Nakamura, Yusuke [1 ]
Daigo, Yataro [1 ]
机构
[1] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab,Minato Ku, Tokyo 1088639, Japan
[2] Hiroshima Univ, Grad Sch Biomed Sci, Dept Mol & Internal Med, Hiroshima, Japan
[3] Hiroshima Univ, Grad Sch Biomed Sci, Dept Mol Pathol, Hiroshima, Japan
[4] Hiroshima Univ, Grad Sch Biomed Sci, Dept Pathol, Hiroshima, Japan
[5] Saitama Canc Ctr, Dept Thorac Surg, Saitama, Japan
[6] Kanagawa Canc Ctr, Div Thorac Surg, Kanagawa, Japan
[7] Kanagawa Canc Ctr, Mol Pathol & Genet Div, Kanagawa, Japan
[8] Keiyukai Sapporo Hosp, Sapporo, Hokkaido, Japan
关键词
D O I
10.1158/0008-5472.CAN-07-3243
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of 81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely diagnosed. In most cases, there was no correlation between serum LY6K and conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified 64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and CYFRA 21-1 increased sensitivity in the detection of lung squamous cell carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with small interfering RNAs resulted in growth suppression of the lung and esophageal cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for cancer treatment.
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收藏
页码:11601 / 11611
页数:11
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