Sperm-Associated Antigen 9, a Novel Biomarker for Early Detection of Breast Cancer

Abstract

To date, there have been no tumor biomarkers validated and incorporated into oncologic practice for the early diagnosis of breast cancer. Recently, we showed that sperm-associated antigen 9 (SPAG9), a member of cancer testis (CT) antigen family, is associated with ovarian carcinomas. In the present study, we investigated SPAG9 expression and humoral immune response in breast cancer. We further evaluated the diagnostic potential of autoantibodies to SPAG9 protein in various stages, grades, and histotypes of breast cancer. We analyzed the association of SPAG9 immunoreactivity score (IRS) with predicted risk of breast cancer recurrence over 10 years. Our reverse transcription-PCR and immunohistochemical analyses revealed SPAG9 expression in 88% breast cancer specimens independent of tumor stages and grades. Further, the humoral immune response against SPAG9 was detected in 80% breast cancer patients with SPAG9-expressing tumors. The linear regression modeling predicted a direct relationship between presence of lymphovascular invasion and high SPAG9 IRS, whereas the univariate and multivariate logistic regression models predicted a strong association of SPAG9 IRS with tumor grade. Further, our data indicated a significant higher trend of SPAG9 IRS with the predicted high risk of breast cancer recurrence. The present investigation reports for the first time SPAG9 expression and humoral immune response in early stages and low-grade breast cancer. Although our data indicated that autoantibodies against SPAG9 represent a promising approach for the development of biomarker, further large-scale validation studies are required to establish its potential use in early diagnosis and monitoring of breast cancer recurrence. (Cancer Epidemiol Biomarkers Prev 2009;18(2):630 -9)

Sperm-Associated Antigen 9 is a Promising marker for Early Diagnosis of Endometrial Cancer

“…Their restricted gene expression in various malignancies has led the researchers to investigate their potential as a target for immunotherapeutic modalities, such as antigen based vaccination and antigen directed immunotherapy (Suri, 2006). Moreover, humoral and cellular immune responses to CT antigens have directed attention to their potential in early diagnosis of cancer (Suri, 2006, Garg et al, 2009a, Garg et al, 2009b, Kanojia et al, 2009). …”

“…SPAG9 gene is located at the chromosome 17q21, which is a region involved in amplification and expression of cancer-related genes (Jagadish et al, 2005b). Although it was originally thought to be expressed exclusively in testis, ongoing research revealed SPAG9 expression in numerous tumors originating from various sites and organs such as brain, thyroid, breast, lung, kidney, colon, ovary, cervix, and endometrium (Garg et al, 2008, Garg et al, 2009a, Garg et al, 2009b, Kanojia et al, 2009, Kanojia et al, 2011, Yu et al, 2012, Wang et al, 2013, Yi et al, 2013. In a study by Garg et al (2007), SPAG9 expression and host immune responses were investigated in epithelial ovarian cancer (EOC) specimens and human ovarian cancer cell lines (Garg et al, 2007).…”

“…SPAG9 has been recently proposed as a novel biomarker for early diagnosis Eralp Baser 1 , Cihan Togrul 2 , Emre Ozgu 1 , Sevgi Ayhan 1 , Mete Caglar 1 , Salim Erkaya 1 , Tayfun Gungor 1 of several human tumors, including ovarian, cervical and breast cancer (Garg et al, 2007, Garg et al, 2009a, Kanojia et al, 2009. It is also expressed in endometrial cancer tissue, however its clinical value remains to be clarified (Yu et al, 2012).…”

Sperm-Associated Antigen 9 Is a Novel Biomarker for Colorectal Cancer and Is Involved in Tumor Growth and Tumorigenicity

“…6,12 Cancer-specific alternatively spliced mRNAs and protein isoforms may be used as cancer biomarkers. Our recent study demonstrated SPAG9 expression and its association with clinicopathological characteristics of tumors in renal cell carcinoma, 13 epithelial ovarian cancer, 14 breast cancer, 15 cervical carcinoma, 16 and thyroid cancer. 17 These findings suggest that SPAG9 may have a role in early spread of disease.…”

A novel cancer testis antigen target A-kinase anchor protein (AKAP4) for the early diagnosis and immunotherapy of colon cancer

“…8,9 Interestingly, none of these studies reported humoral response against CT antigens except OY-TES-1 which demonstrated that only 9.6% (7/73) patients generated auto-antibodies. 7 The most studied SPAG9 in various malignancies [20][21][22][23][24][25] was also shown to be associated with CRC in various stages and histotypes. 6 SPAG9 was also found to be highly immunogenic and demonstrated humoral response in CRC patients.…”