三种癌—睾丸抗原基因在脑膜瘤中的表达研究
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摘要
目的：探讨三种癌-睾丸抗原用于脑膜瘤免疫治疗的可能性。
方法：采用逆转录-聚合酶链反应(RT-PCR)技术，检测41例人脑膜瘤组织及29例正常组织中三种癌-睾丸抗原(SCP-1、NY-SAR-35和OY-TES-1)的表达情况，并结合癌-睾丸抗原的表达与临床参数进行统计学分析。
结果：SCP-1在所检测的脑膜瘤和正常组织均不表达：NY-SAR-35在正常组织和脑膜瘤组织中的表达频率分别为13.79％(4／29)和36.59％(15／41)，两者比较有显著性差异(p＜0.05)。在14种不同器官的正常组织中，3种表达NY－SAR－35。OY-TES－1在正常组织和脑膜瘤组织中的表达频率分别为68.97％(20／29)和39.02％(16／41)，两者比较有显著性差异(D＜0.05)。在14种不同器官的组织中，12种表达OY-TES-1。NY-SAR-35和OY-TES-1的表达频率分别与脑膜瘤病人的年龄、性别、肿瘤大小、组织类型和临床病理分级进行比较，均无统计学意义(p＞0.05)。
结论：NY-SAR-35在脑膜瘤组织中有较高表达频率，提示它有可能成为脑膜瘤免疫治疗的靶抗原：考虑剑OY-TES-1在正常组织中广泛表达，它是否为真正的痛-睾丸抗原尚需进一步研究。
OBJECTIVE: The purpose of this study was to determine the potential of three cancer testis antigens (CTA) as vaccines for human meningioma.
METHODS: Forty one specimens of human meningioma and twenty nine specimens of human normal tissues were analyzed for the expression of three CTA genes (SCP-1, NY-SAR-35 and OY-TES-1) by Reverse Transcriptase Chain Reaction (RT-PCR). Correlation between the expression of CTA genes and clinical data was evaluated.
RESULTS: All of meningiomas and normal tissues were negative for SCP-1. The expressive frequency of NY-SAR-35 in normal and meningioma tissues was 13.79% (4/29) and 36.59% (15/41), respectively. There was significant difference for the expressive frequency of NY-SAR-35 in both normal and meningioma tissues (p<0. 05). Of 14 specimens of normal tissues from different organs, 3 expressed NY-SAR-35. As to OY-TES-1, the expressive frequency in normal and meningioma tissues was 68.97% (20/29) and 39.02% (16/41), respectively. Significant difference for the expressive frequency of OY-TES-1 in both normal and meningioma tissues has been showed (p<0. 05). Of 14 specimens of normal tissues from different organs, 12 were positive in OY-TES-1. There was no statistic significance for the expression of NY-SAR-35 and OY-TES-1 correlated with patients' age, sex, histological subtype and clinical pathological grade of meningioma (p>0. 05).
CONCLUSION: With higher expressive frequency in meningioma tissues, NY-SAR-35 might be a potential promising target for immunotherapy of meningioma. The fact of broad expression of OY-TES-1 in series
of normal tissues has been considered, and whether OY-TES-1 was a true cancer testis antigen or not has to be further determined.
方法：采用逆转录-聚合酶链反应(RT-PCR)技术，检测41例人脑膜瘤组织及29例正常组织中三种癌-睾丸抗原(SCP-1、NY-SAR-35和OY-TES-1)的表达情况，并结合癌-睾丸抗原的表达与临床参数进行统计学分析。
结果：SCP-1在所检测的脑膜瘤和正常组织均不表达：NY-SAR-35在正常组织和脑膜瘤组织中的表达频率分别为13.79％(4／29)和36.59％(15／41)，两者比较有显著性差异(p＜0.05)。在14种不同器官的正常组织中，3种表达NY－SAR－35。OY-TES－1在正常组织和脑膜瘤组织中的表达频率分别为68.97％(20／29)和39.02％(16／41)，两者比较有显著性差异(D＜0.05)。在14种不同器官的组织中，12种表达OY-TES-1。NY-SAR-35和OY-TES-1的表达频率分别与脑膜瘤病人的年龄、性别、肿瘤大小、组织类型和临床病理分级进行比较，均无统计学意义(p＞0.05)。
结论：NY-SAR-35在脑膜瘤组织中有较高表达频率，提示它有可能成为脑膜瘤免疫治疗的靶抗原：考虑剑OY-TES-1在正常组织中广泛表达，它是否为真正的痛-睾丸抗原尚需进一步研究。
OBJECTIVE: The purpose of this study was to determine the potential of three cancer testis antigens (CTA) as vaccines for human meningioma.
METHODS: Forty one specimens of human meningioma and twenty nine specimens of human normal tissues were analyzed for the expression of three CTA genes (SCP-1, NY-SAR-35 and OY-TES-1) by Reverse Transcriptase Chain Reaction (RT-PCR). Correlation between the expression of CTA genes and clinical data was evaluated.
RESULTS: All of meningiomas and normal tissues were negative for SCP-1. The expressive frequency of NY-SAR-35 in normal and meningioma tissues was 13.79% (4/29) and 36.59% (15/41), respectively. There was significant difference for the expressive frequency of NY-SAR-35 in both normal and meningioma tissues (p<0. 05). Of 14 specimens of normal tissues from different organs, 3 expressed NY-SAR-35. As to OY-TES-1, the expressive frequency in normal and meningioma tissues was 68.97% (20/29) and 39.02% (16/41), respectively. Significant difference for the expressive frequency of OY-TES-1 in both normal and meningioma tissues has been showed (p<0. 05). Of 14 specimens of normal tissues from different organs, 12 were positive in OY-TES-1. There was no statistic significance for the expression of NY-SAR-35 and OY-TES-1 correlated with patients' age, sex, histological subtype and clinical pathological grade of meningioma (p>0. 05).
CONCLUSION: With higher expressive frequency in meningioma tissues, NY-SAR-35 might be a potential promising target for immunotherapy of meningioma. The fact of broad expression of OY-TES-1 in series
of normal tissues has been considered, and whether OY-TES-1 was a true cancer testis antigen or not has to be further determined.
引文
1．黄文清．神经肿瘤病理学(第二版)．北京：军事医学科学出版社，200 1：479
2. Sawamura Y, de Tribolet N. Immunobiology of brain tumor. Adv Tech Stand Neurosurg, 1990,17:3
3. Pollack IF, Okada H, Chambers WH. Exploitation of immune mechanisms in the treatment of central nervous system cancer. Semin Pediatr Neurol, 2000,7:131
4. Yoshida S, Tanaka R, Takai N, et al. Local administration of autologous lymphokine-activated ceils and recombinant interleukin 2 to patients with malignant brain tumors. Cancer res, 1988,48:5011
5. Chen YT, Scanlan MJ, Sahin U, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A, 1997,94:1914
6. Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: Review, standardization, and commentary. Cancer Immunity, 2004,4:1
7. Jager E, Gnjatic S, Nagata Y, et al. Induction of primary NY-ESO-limminity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancer. Proc Natl Acad Sci U S A, 2000,97:12198
8. SahinU, Koslowski M, Tureci O, et al. Expression of cancer testis genes in human brain tumors. Clin Cancer Res, 2000,6:3916
9. OnoT, KurashigeT, Harada N, et al. Identification ofproacrosin binding protein sp32 precursor as a human cancer/testis antigen. Proc Natl Acad Sci U S A, 2001,98:3282
10. Lee SY, Obata Yuichi, Yoshida M, et al. Immunomic analysis of human sarcoma. Proc Natl Acad Sci U S A, 2003,100:2651
11. Oure AO, Stockert E, Arden KC, et al. CT10: a new cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representational difference analysis. Int J Cancer, 2000,85:726
12. Tureci O, Dahin U, Koslowski M, et al. Identification of a meiosis-specific protein as a new member of the class of cancer/testis antigens. Proc Natl Acad Sci U S A, 1998,95:5211
13. Sahin U, Tureci O, Schmitt H, et al. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A, 1995,92:11810
14. Sage J, Martin L, Cuzin F, et al. cDNA sequence of the murine synaptonemal complex protein 1 (SCP1) Biochim Biophys Acta, 1995,1263:258
15. Hoffmann W, Hauser F. The P-domain or trefoil motif: a role in renewal and pathology of mucous epithelia? Trends Biochem Sci, 1993,18:239
16. Lethe B, Lucas S, Michaux L, et al. LAGE-1, a new gene with tumor specificity. Int J Cancer, 1998,76:903
17. KubuschokB, XieX, Jesnowski R, et al. ExpressionoFcancer testis antigens in pancreatic carcinoma cell lines, pancreatic adenocarcinoma and chronic pancreatitis. Int 7 Cancer, 2004,109:568
18. Jager E, Ringhoffer M, Altannsberger M, et al. Immunoselection in vivo: independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma. Int J Cancer, 1997,71:142
19. Zendman AJW, Ruiter D, Goos NP. Cancer/testis-associated genes: identification, expression profile, and putative function. Cellu Phys, 2003,194:272
2. Sawamura Y, de Tribolet N. Immunobiology of brain tumor. Adv Tech Stand Neurosurg, 1990,17:3
3. Pollack IF, Okada H, Chambers WH. Exploitation of immune mechanisms in the treatment of central nervous system cancer. Semin Pediatr Neurol, 2000,7:131
4. Yoshida S, Tanaka R, Takai N, et al. Local administration of autologous lymphokine-activated ceils and recombinant interleukin 2 to patients with malignant brain tumors. Cancer res, 1988,48:5011
5. Chen YT, Scanlan MJ, Sahin U, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A, 1997,94:1914
6. Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: Review, standardization, and commentary. Cancer Immunity, 2004,4:1
7. Jager E, Gnjatic S, Nagata Y, et al. Induction of primary NY-ESO-limminity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancer. Proc Natl Acad Sci U S A, 2000,97:12198
8. SahinU, Koslowski M, Tureci O, et al. Expression of cancer testis genes in human brain tumors. Clin Cancer Res, 2000,6:3916
9. OnoT, KurashigeT, Harada N, et al. Identification ofproacrosin binding protein sp32 precursor as a human cancer/testis antigen. Proc Natl Acad Sci U S A, 2001,98:3282
10. Lee SY, Obata Yuichi, Yoshida M, et al. Immunomic analysis of human sarcoma. Proc Natl Acad Sci U S A, 2003,100:2651
11. Oure AO, Stockert E, Arden KC, et al. CT10: a new cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representational difference analysis. Int J Cancer, 2000,85:726
12. Tureci O, Dahin U, Koslowski M, et al. Identification of a meiosis-specific protein as a new member of the class of cancer/testis antigens. Proc Natl Acad Sci U S A, 1998,95:5211
13. Sahin U, Tureci O, Schmitt H, et al. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A, 1995,92:11810
14. Sage J, Martin L, Cuzin F, et al. cDNA sequence of the murine synaptonemal complex protein 1 (SCP1) Biochim Biophys Acta, 1995,1263:258
15. Hoffmann W, Hauser F. The P-domain or trefoil motif: a role in renewal and pathology of mucous epithelia? Trends Biochem Sci, 1993,18:239
16. Lethe B, Lucas S, Michaux L, et al. LAGE-1, a new gene with tumor specificity. Int J Cancer, 1998,76:903
17. KubuschokB, XieX, Jesnowski R, et al. ExpressionoFcancer testis antigens in pancreatic carcinoma cell lines, pancreatic adenocarcinoma and chronic pancreatitis. Int 7 Cancer, 2004,109:568
18. Jager E, Ringhoffer M, Altannsberger M, et al. Immunoselection in vivo: independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma. Int J Cancer, 1997,71:142
19. Zendman AJW, Ruiter D, Goos NP. Cancer/testis-associated genes: identification, expression profile, and putative function. Cellu Phys, 2003,194:272