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.