Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas.
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.
Ishikawa
Nobuhisa
N
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Takano
Atsushi
A
Yasui
Wataru
W
Inai
Kouki
K
Nishimura
Hitoshi
H
Ito
Hiroyuki
H
Miyagi
Yohei
Y
Nakayama
Haruhiko
H
Fujita
Masahiro
M
Hosokawa
Masao
M
Tsuchiya
Eiju
E
Kohno
Nobuoki
N
Nakamura
Yusuke
Y
Daigo
Yataro
Y
D000950:Antigens, Ly / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C525725:LY6K protein, human; D009363:Neoplasm Proteins