Sperm-Associated Antigen 9: A Novel Diagnostic Marker for Thyroid cancer

Context: Cancer-testis antigens are the unique class of testis proteins expressed in tumor but not healthy tissue except testis and might represent ideal targets for the development of novel diagnostics and therapeutic methods in thyroid cancer, which is the most common malignancy of the endocrine system. Objective: Our objective was to investigate the clinical relevance of cancer-testis antigen sperm-associated antigen 9 (SPAG9) as early diagnostic and therapeutic target in thyroid cancer. Design, Setting, and Subjects: SPAG9 gene and protein expression was determined in thyroid cancer cell lines in 138 thyroid tumor specimens, 60 adjacent noncancerous tissues (ANCT), 22 multinodular goiters (nonneoplastic hyperplasia), and 20 follicular adenoma tissue samples by RT-PCR, in situ RNA hybridization, and immunohistochemistry. Gene silencing approach was used to examine the effects of suppression of SPAG9 protein on cellular growth and colony formation. Humoral immune response against SPAG9 in thyroid cancer patients was analyzed using ELISA. Results: SPAG9 mRNA and protein expression was detected in 78% of the thyroid cancer patients but not multiple goiters and follicular adenoma disease patients. It is interesting to note that majority of early-stage (T1) thyroid cancer patients exhibited higher antibody response against SPAG9. Small interfering RNA-mediated knockdown of SPAG9 expression in thyroid cancer cell significantly reduced cellular growth and colony formation. Conclusions: SPAG9 expression may play a role in cellular growth and thyroid carcinogenesis. These findings support a potential role for SPAG9 as diagnostic biomarker as well as a possible therapeutic target in thyroid cancer treatment. (J Clin Endocrinol Metab 94: 4613-4618, 2009)