Characterization of a cancer/testis (CT) antigen gene family capable of eliciting humoral response in cancer patients

Parmigiani, Raphael B.; Bettoni, Fabiana; Vibranovski, Maria D.; Lopes, Marilene H.; Martins, Waleska K.; Cunha, Isabela Werneck da; Soares, Fernando Augusto; Simpson, Andrew J.G.; Souza, Sandro J. de; Camargo, Anamaria A.

doi:10.1073/pnas.0608853103

Cited by 35 publications

(25 citation statements)

References 37 publications

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“…When we compared immune response against SPAG9 with the other known CT antigens, it is important to note that NY-ESO-1, SCP-1, and SSX-2 showed humoral immune response only in 4%, 6%, and 1% breast cancer patients, respectively (11). In yet another study, antibody response against CT antigen CTSP-1 was observed only in 16.6% of breast cancer patients (38). However, our study reveals that 88% of early-stage (I and II) cancer patients and 78% of low-grade (grade 1) cancer patients generated immune response against SPAG9, suggesting strong immunogenicity of SPAG9 protein in breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

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

Kanojia

Garg

Gupta³

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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)

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Section: Discussionmentioning

confidence: 99%

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

Kanojia

Garg

Gupta³

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…CTAs are restricted in normal tissues to germ cells of the testis, with occasional expression in female reproductive organs, and are expressed in histologically different types of malignant human tumors [1][2][3][4]. The tumor restricted expression pattern of CTAs makes them an interesting target for immunotherapeutic approaches [3,5].…”

Section: Introductionmentioning

confidence: 99%

“…Cor1 family members such as X-linked lymphocyte regulated protein (XLR), Xlr-related meiosis regulated protein (XMR), and synaptonemal complex protein 3 (SCP3) are typical CTAs [1].…”

Section: Introductionmentioning

confidence: 99%

Synaptonemal complex protein 3 is a prognostic marker in cervical cancer

Cho

Kim

Chay

et al. 2014

Gynecologic Oncology

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Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P,0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.

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“…Thus far, an increasing number of CT antigens have been cloned and identified by various approaches, such as CAGE and HCA587 by SEREX, 8,9 CT10 by RDA, 10 CTSP-1, FATE/BJ-HCC-2 and TPTE/BJ-HCC-5 by database mining. 11,12 In this work, suppression subtractive hybridization (SSH) was performed to identify tumor specific antigen encoding genes in hepatocellular cancer (HCC) samples. PLAC1 (PLACenta-specific 1), a known trophoblast-specific gene, was one of the genes found to be highly expressed in HCC tissues but not in paired noncancerous tissues.…”

mentioning

confidence: 99%

Plac1 is a tumor‐specific antigen capable of eliciting spontaneous antibody responses in human cancer patients

Dong

Peng

et al. 2008

Intl Journal of Cancer

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Immunoselection and tumor evasion constitutes one of the major obstacles in cancer immunotherapy. A potential solution to this problem is the development of polyvalent vaccines, and the identification of more tumor-specific antigens is a prerequisite for the development of cancer vaccines. To identify novel tumor-specific antigens, suppression subtractive hybridization (SSH) was performed to isolate genes differentially expressed in human hepatocellular cancer (HCC) tissues. PLAC1 (PLACenta-specific 1) was one of the genes identified highly expressed in HCC tissues but not in paired noncancerous tissues. Further analyses revealed its expression in several other types of cancer tissues as well as tumor cell lines, but not in normal tissues except for placenta. Among HCC samples tested, 32% (22/69) showed PLAC1 mRNA expression while the protein was detected in 23.3% (7/30). A serological survey revealed that 3.8% (4/101) of HCC patients had anti-PLAC1 antibody response, suggesting the immunogenicity of PLAC1 in HCC patients. PLAC1 represents a new class of tumor associated antigen with restricted expression in placenta and cancer tissues, that may serve as a target for cancer vaccination.

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Characterization of a cancer/testis (CT) antigen gene family capable of eliciting humoral response in cancer patients

Cited by 35 publications

References 37 publications

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

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

Synaptonemal complex protein 3 is a prognostic marker in cervical cancer

Plac1 is a tumor‐specific antigen capable of eliciting spontaneous antibody responses in human cancer patients

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