Garg Manoj, Chaurasiya Dipak, Rana Ritu, Jagadish Nirmala, Kanojia Deepika, Dudha Namrata, Kamran Neha, Salhan Sudha, Bhatnagar Amar, Suri Sushma, Gupta Anju, Suri Anil
Genes and Proteins Laboratory, National Institute of Immunology, New Delhi, India.
Clin Cancer Res. 2007 Mar 1;13(5):1421-8. doi: 10.1158/1078-0432.CCR-06-2340.
Cancer testis antigens are a group of tumor antigens with gene expression restricted to male germ cells in the testis and in various cancerous tissues. Recently, we reported a novel testis-specific sperm-associated antigen 9 (SPAG9) gene, a new member of the c-Jun NH(2)-terminal kinase-interacting protein family, having functional role in sperm-egg fusion and mitogen-activated protein kinase signaling pathway. National Center for Biotechnology Information Blast searches revealed SPAG9 nucleotide sequence similarities with expressed sequence tags of various cancerous tissues. In an effort to examine the clinical utility of SPAG9, we investigated the SPAG9 mRNA and protein expression in epithelial ovarian cancer (EOC). Humoral immune response to SPAG9 was also evaluated in EOC patients.
We determined the expression profile of SPAG9 transcript by reverse transcription-PCR and RNA in situ hybridization and SPAG9 protein expression by immunohistochemistry in EOC specimens and human ovarian cancer cell lines. Using ELISA and Western blotting, we analyzed specific antibodies for SPAG9 in sera from patients with EOC.
SPAG9 mRNA and protein expression was detected in 90% of EOC tissues and in all three human ovarian cancer cell lines. Specific SPAG9 antibodies were detected in 67% of EOC patients and not in sera from healthy individuals.
Our findings indicate that SPAG9 is highly expressed in EOC and immunogenic in patients. Humoral immune response against SPAG9 in early stages of EOC suggests its important role in early diagnostics. These results collectively suggest that SPAG9, a novel member of cancer testis antigen family, could be a potential target for the development of diagnostic and therapeutic methods in EOC.
癌睾丸抗原是一组肿瘤抗原，其基因表达局限于睾丸中的雄性生殖细胞以及各种癌组织。最近，我们报道了一种新的睾丸特异性精子相关抗原9（SPAG9）基因，它是c-Jun NH(2)-末端激酶相互作用蛋白家族的新成员，在精卵融合和丝裂原活化蛋白激酶信号通路中具有功能作用。美国国立生物技术信息中心的Blast搜索显示，SPAG9核苷酸序列与各种癌组织的表达序列标签相似。为了研究SPAG9的临床应用价值，我们调查了上皮性卵巢癌（EOC）中SPAG9 mRNA和蛋白的表达情况。还评估了EOC患者对SPAG9的体液免疫反应。
我们通过逆转录PCR和RNA原位杂交确定了EOC标本和人卵巢癌细胞系中SPAG9转录本的表达谱，并通过免疫组织化学确定了SPAG9蛋白的表达。使用酶联免疫吸附测定（ELISA）和蛋白质印迹法，我们分析了EOC患者血清中针对SPAG9的特异性抗体。
在90%的EOC组织和所有三个人卵巢癌细胞系中检测到SPAG9 mRNA和蛋白表达。在67%的EOC患者中检测到特异性SPAG9抗体，而在健康个体的血清中未检测到。
我们的研究结果表明，SPAG9在EOC中高表达且在患者中具有免疫原性。EOC早期针对SPAG9的体液免疫反应表明其在早期诊断中具有重要作用。这些结果共同表明，癌睾丸抗原家族的新成员SPAG9可能是EOC诊断和治疗方法开发的潜在靶点。
