Tuberc Respir Dis.  2011 Apr;70(4):315-322.

Expression of MAGE A 1-6 and SSX 1-9 Genes in the Sputum and Cancer Tissue of the Lung Cancer Patients

Affiliations
  • 1Leeyeunjae Meck Clinic, Daegu, Korea.
  • 2Department of Thoracic and Cardiovascular Surgery, Yeungnam University College of Medicine, Daegu, Korea. jclee@med.yu.ac.kr
  • 3Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.

Abstract

BACKGROUND
A variety of diagnostic modalities for lung cancer have been developed. To achieve efficient and early detection of lung cancer, we tried to measure the expression rates of the melanoma associated gene (MAGE) and synovial sarcoma on X chromosome (SSX) genes.
METHODS
We designed primers for the SSX gene. In addition to the pre-developed MAGE A primer, using an SSX gene primer was attempted to increase the detection rate. We obtained cancer tissues and cancer-free lung tissues from resected lung, sputum from lung cancer patients who had not undergone surgery, and sputum from healthy people and patients with benign intrathoracic diseases.
RESULTS
The sensitivity of the MAGE or SSX gene RT-PCR to identifying cancer tissue of the 69 lung cancer patients was 95.2% for squamous cell carcinoma (scc), 87.0% for adenocarcinoma, and 100% for small cell carcinoma. The mean sensitivity value was 94.2% (p=0.001). For adenocarcinoma, the additional use of the SSX gene resulted in a higher expression rate than MAGE alone (87% vs. 69.6%). The expression rate for the cancer-free lung tissue was 14.3% in scc, 17.4% in adenocarcinoma, and 25.0% in small cell carcinoma. In the induced sputum of 49 lung cancer patients who had not undergone surgery, the expression rate for one of the two genes was 65.5%. The expression rate for the sputum of healthy people and benign intrathoracic diseases by MAGE or SSX gene reverse transcription polymerase chain reaction (RT-PCR) was 3.8% and 17.7%.
CONCLUSION
Detecting lung cancer using the expression of MAGE and SSX genes in lung cancer tissue has high sensitivity.

Keyword

Lung Neoplasms; Genes

MeSH Terms

Adenocarcinoma
Carcinoma, Small Cell
Carcinoma, Squamous Cell
Humans
Lung
Lung Neoplasms
Melanoma
Polymerase Chain Reaction
Reverse Transcription
Sarcoma, Synovial
Sputum
X Chromosome

Figure

  • Figure 1 Electrophoresis of MAGE (A), SSX gene (B) and GAPD (C) RT-PCR products in ten sputa of lung cancer patients. MAGE: melanoma associated gene; SSX: synovial sarcoma on X chromosome; GAPD: glyceraldehyde phosphate dehydrogenase; RT-PCR: reverse transcription polymerase chain reaction; SM: size markers.


Reference

1. Korea Central Cancer Registry. Republic of Korea. 2002 Annual report of the Korea central cancer registry: based on registered data from 139 hospitals. 2005. Seoul: Ministry of Health and Welfare.
2. Kawahara M. Screening for lung cancer. Curr Opin Oncol. 2004. 16:141–145.
3. McWilliams A, Lam S. Lung cancer screening. Curr Opin Pulm Med. 2005. 11:272–277.
4. Lee P, Sutedja TG. Lung cancer screening: has there been any progress? Computed tomography and autofluorescence bronchoscopy. Curr Opin Pulm Med. 2007. 13:243–248.
5. Greenberg AK, Lee MS. Biomarkers for lung cancer: clinical uses. Curr Opin Pulm Med. 2007. 13:249–255.
6. Lee KH, Shin KC, Lee CH, Jheon SH, Jeon CH. Detection of lung cancer using MAGE A1-6 and SSX4 RT-PCR expression profiles in the bronchial wash fluid. Cancer Res Treat. 2007. 39:69–73.
7. Phillips M, Cataneo RN, Cummin AR, Gagliardi AJ, Gleeson K, Greenberg J, et al. Detection of lung cancer with volatile markers in the breath. Chest. 2003. 123:2115–2123.
8. Poli D, Carbognani P, Corradi M, Goldoni M, Acampa O, Balbi B, et al. Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study. Respir Res. 2005. 6:71.
9. Mecklenburg I, Stratakis DF, Huber RM, Häussinger K, Morresi-Hauf A, Riethmüller G, et al. Detection of melanoma antigen-A expression in sputum and bronchial lavage fluid of patients with lung cancer. Chest. 2004. 125:5 Suppl. 164S–166S.
10. Tajima K, Obata Y, Tamaki H, Yoshida M, Chen YT, Scanlan MJ, et al. Expression of cancer/testis (CT) antigens in lung cancer. Lung Cancer. 2003. 42:23–33.
11. Sugita M, Geraci M, Gao B, Powell RL, Hirsch FR, Johnson G, et al. Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma. Cancer Res. 2002. 62:3971–3979.
12. Wu Y, Li Y, Lin Y. Expression of MAGE-12 in lung cancer. Lung Cancer. 2002. 35:95.
13. Park JW, Kwon TK, Kim IH, Sohn SS, Kim YS, Kim CI, et al. A new strategy for the diagnosis of MAGE-expressing cancers. J Immunol Methods. 2002. 266:79–86.
14. Jheon S, Hyun DS, Lee SC, Yoon GS, Jeon CH, Park JW, et al. Lung cancer detection by a RT-nested PCR using MAGE A1--6 common primers. Lung Cancer. 2004. 43:29–37.
15. Gure AO, Türeci O, Sahin U, Tsang S, Scanlan MJ, Jäger E, et al. SSX: a multigene family with several members transcribed in normal testis and human cancer. Int J Cancer. 1997. 72:965–971.
16. Türeci O, Chen YT, Sahin U, Güre AO, Zwick C, Villena C, et al. Expression of SSX genes in human tumors. Int J Cancer. 1998. 77:19–23.
17. Güre AO, Wei IJ, Old LJ, Chen YT. The SSX gene family: characterization of 9 complete genes. Int J Cancer. 2002. 101:448–453.
18. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991. 254:1643–1647.
19. De Plaen E, Arden K, Traversari C, Gaforio JJ, Szikora JP, De Smet C, et al. Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics. 1994. 40:360–369.
20. Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001. 61:5544–5551.
21. Jungbluth AA, Busam KJ, Kolb D, Iversen K, Coplan K, Chen YT, et al. Expression of MAGE-antigens in normal tissues and cancer. Int J Cancer. 2000. 85:460–465.
22. Brichard VG, Lejeune D. GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development. Vaccine. 2007. 25:Suppl 2. B61–B71.
23. Yang B, O'Herrin SM, Wu J, Reagan-Shaw S, Ma Y, Bhat KM, et al. MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res. 2007. 67:9954–9962.
24. Törnkvist M, Brodin B, Bartolazzi A, Larsson O. A novel type of SYT/SSX fusion: methodological and biological implications. Mod Pathol. 2002. 15:679–685.
25. Sahin U, Koslowski M, Türeci O, Eberle T, Zwick C, Romeike B, et al. Expression of cancer testis genes in human brain tumors. Clin Cancer Res. 2000. 6:3916–3922.
26. Kubuschok B, Xie X, Jesnowski R, Preuss KD, Romeike BF, Neumann F, et al. Expression of cancer testis antigens in pancreatic carcinoma cell lines, pancreatic adenocarcinoma and chronic pancreatitis. Int J Cancer. 2004. 109:568–575.
27. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin. Cancer. 1953. 6:963–968.
28. Zheng W, Blot WJ, Liao ML, Wang ZX, Levin LI, Zhao JJ, et al. Lung cancer and prior tuberculosis infection in Shanghai. Br J Cancer. 1987. 56:501–504.
29. Kurasawa T. The coexistence of pulmonary tuber culosis and lung cancer. Nippon Rinsho. 1998. 56:3167–3170.
30. Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE, Muhm JR. Lung cancer screening: the Mayo program. J Occup Med. 1986. 28:746–750.
31. Fraire AE, Underwood RD, McLarty JW, Greenberg SD. Conventional respiratory cytology versus fine needle aspiration cytology in the diagnosis of lung cancer. Acta Cytol. 1991. 35:385–388.
32. Frost JK, Ball WC Jr, Levin ML, Tockman MS, Baker RR, Carter D, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Respir Dis. 1984. 130:549–554.
Full Text Links
  • TRD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr