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. 1999 Feb;79(3-4):565–569. doi: 10.1038/sj.bjc.6690089

Expression of pyrimidine nucleoside phosphorylase mRNA plays an important role in the prognosis of patients with oesophageal cancer

M Yamagata 1, M Mori 1, K Mimori 1, K-I Mafune 2, Y Tanaka 3, H Ueo 4, T Akiyoshi 1
PMCID: PMC2362421  PMID: 10027331

Abstract

To clarify the significance of the expression of pyrimidine nucleoside phosphorylase (PyNPase) mRNA as a predictive factor for the prognosis of patients with oesophageal carcinoma, the PyNPase mRNA in the tumours and normal tissues from 55 resected cases of oesophageal carcinoma was examined by a reverse transcription polymerase chain reaction (RT-PCR). As a result, a positive correlation was observed between the tumour/normal (T/N) ratio of the expression of PyNPase mRNA by RT-PCR and that of the enzyme activity of PyNPase based on the findings of an enzyme linked immunosolvent assay (r = 0.594, P = 0.009). The T/N ratio of the expression of PyNPase mRNA was significantly higher in the cases with lymph vessel invasion (P = 0.013), lymph node metastasis (P = 0.0016), and an advanced stage of the disease (P = 0.021) than those without these factors. The patients with a higher T/N ratio of PyNPase mRNA showed significantly worse prognosis than those with a lower T/N ratio (P = 0.023 with log-rank tests). A multivariate analysis for the cumulative survival rates revealed that a high T/N ratio of the expression of PyNPase mRNA was independently related to a poor prognosis. These findings suggested that the determination of PyNPase mRNA by RT-PCR thus appears to be a new useful parameter for identifying both a poor prognosis and a highly malignant potential of oesophageal carcinoma. © 1999 Cancer Research Campaign

Keywords: pyrimidine nucleoside phosphorylase, oesophagus, carcinoma, human, reverse transcription polymerase chain reaction

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Selected References

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  1. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  2. Eda H., Fujimoto K., Watanabe S., Ura M., Hino A., Tanaka Y., Wada K., Ishitsuka H. Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 5'-deoxy-5-fluorouridine. Cancer Chemother Pharmacol. 1993;32(5):333–338. doi: 10.1007/BF00735915. [DOI] [PubMed] [Google Scholar]
  3. Furukawa T., Yoshimura A., Sumizawa T., Haraguchi M., Akiyama S., Fukui K., Ishizawa M., Yamada Y. Angiogenic factor. Nature. 1992 Apr 23;356(6371):668–668. doi: 10.1038/356668a0. [DOI] [PubMed] [Google Scholar]
  4. Giatromanolaki A., Koukourakis M. I., Comley M., Kaklamanis L., Turley H., O'Byrne K., Harris A. L., Gatter K. C. Platelet-derived endothelial cell growth factor (thymidine phosphorylase) expression in lung cancer. J Pathol. 1997 Feb;181(2):196–199. doi: 10.1002/(SICI)1096-9896(199702)181:2<196::AID-PATH763>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  5. Horikoshi T., Danenberg K. D., Stadlbauer T. H., Volkenandt M., Shea L. C., Aigner K., Gustavsson B., Leichman L., Frösing R., Ray M. Quantitation of thymidylate synthase, dihydrofolate reductase, and DT-diaphorase gene expression in human tumors using the polymerase chain reaction. Cancer Res. 1992 Jan 1;52(1):108–116. [PubMed] [Google Scholar]
  6. Imazano Y., Takebayashi Y., Nishiyama K., Akiba S., Miyadera K., Yamada Y., Akiyama S., Ohi Y. Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma. J Clin Oncol. 1997 Jul;15(7):2570–2578. doi: 10.1200/JCO.1997.15.7.2570. [DOI] [PubMed] [Google Scholar]
  7. Ishikawa F., Miyazono K., Hellman U., Drexler H., Wernstedt C., Hagiwara K., Usuki K., Takaku F., Risau W., Heldin C. H. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989 Apr 13;338(6216):557–562. doi: 10.1038/338557a0. [DOI] [PubMed] [Google Scholar]
  8. Ishitsuka H., Miwa M., Takemoto K., Fukuoka K., Itoga A., Maruyama H. B. Role of uridine phosphorylase for antitumor activity of 5'-deoxy-5-fluorouridine. Gan. 1980 Feb;71(1):112–123. [PubMed] [Google Scholar]
  9. Kono A., Hara Y., Sugata S., Karube Y., Matsushima Y., Ishitsuka H. Activation of 5'-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors. Chem Pharm Bull (Tokyo) 1983 Jan;31(1):175–178. doi: 10.1248/cpb.31.175. [DOI] [PubMed] [Google Scholar]
  10. Kubota Y., Miura T., Moriyama M., Noguchi S., Matsuzaki J., Takebayashi S., Hosaka M. Thymidine phosphorylase activity in human bladder cancer: difference between superficial and invasive cancer. Clin Cancer Res. 1997 Jun;3(6):973–976. [PubMed] [Google Scholar]
  11. Luccioni C., Beaumatin J., Bardot V., Lefrançois D. Pyrimidine nucleotide metabolism in human colon carcinomas: comparison of normal tissues, primary tumors and xenografts. Int J Cancer. 1994 Aug 15;58(4):517–522. doi: 10.1002/ijc.2910580411. [DOI] [PubMed] [Google Scholar]
  12. Maeda K., Chung Y. S., Ogawa Y., Takatsuka S., Kang S. M., Ogawa M., Sawada T., Onoda N., Kato Y., Sowa M. Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. Br J Cancer. 1996 Apr;73(8):884–888. doi: 10.1038/bjc.1996.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mori M., Mimori K., Inoue H., Barnard G. F., Tsuji K., Nanbara S., Ueo H., Akiyoshi T. Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction. Cancer Res. 1995 Aug 1;55(15):3417–3420. [PubMed] [Google Scholar]
  14. Mori M., Mimori K., Shiraishi T., Tanaka S., Ueo H., Sugimachi K., Akiyoshi T. p27 expression and gastric carcinoma. Nat Med. 1997 Jun;3(6):593–593. doi: 10.1038/nm0697-593. [DOI] [PubMed] [Google Scholar]
  15. Mori M., Mimori K., Ueo H., Karimine N., Barnard G. F., Sugimachi K., Akiyoshi T. Molecular detection of circulating solid carcinoma cells in the peripheral blood: the concept of early systemic disease. Int J Cancer. 1996 Dec 11;68(6):739–743. doi: 10.1002/(SICI)1097-0215(19961211)68:6<739::AID-IJC8>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
  16. Nio Y., Kimura H., Tsubono M., Tseng C. C., Kawabata K., Masai Y., Hayashi H., Meyer C., Fukumoto M., Tobe T. Antitumor activity of 5'-deoxy-5-fluorouridine in human digestive organ cancer xenografts and pyrimidine nucleoside phosphorylase activity in normal and neoplastic tissues from human digestive organs. Anticancer Res. 1992 Jul-Aug;12(4):1141–1146. [PubMed] [Google Scholar]
  17. Nishida M., Hino A., Mori K., Matsumoto T., Yoshikubo T., Ishitsuka H. Preparation of anti-human thymidine phosphorylase monoclonal antibodies useful for detecting the enzyme levels in tumor tissues. Biol Pharm Bull. 1996 Nov;19(11):1407–1411. doi: 10.1248/bpb.19.1407. [DOI] [PubMed] [Google Scholar]
  18. Peto R., Pike M. C. Conservatism of the approximation sigma (O-E)2-E in the logrank test for survival data or tumor incidence data. Biometrics. 1973 Sep;29(3):579–584. [PubMed] [Google Scholar]
  19. Sugimachi K., Watanabe M., Sadanaga N., Ikebe M., Kitamura K., Mori M., Kuwano H. Recent advances in the diagnosis and surgical treatment of patients with carcinoma of the esophagus. J Am Coll Surg. 1994 Apr;178(4):363–368. [PubMed] [Google Scholar]
  20. Takebayashi Y., Akiyama S., Akiba S., Yamada K., Miyadera K., Sumizawa T., Yamada Y., Murata F., Aikou T. Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma. J Natl Cancer Inst. 1996 Aug 21;88(16):1110–1117. doi: 10.1093/jnci/88.16.1110. [DOI] [PubMed] [Google Scholar]
  21. Takebayashi Y., Miyadera K., Akiyama S., Hokita S., Yamada K., Akiba S., Yamada Y., Sumizawa T., Aikou T. Expression of thymidine phosphorylase in human gastric carcinoma. Jpn J Cancer Res. 1996 Mar;87(3):288–295. doi: 10.1111/j.1349-7006.1996.tb00219.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Takebayashi Y., Yamada K., Miyadera K., Sumizawa T., Furukawa T., Kinoshita F., Aoki D., Okumura H., Yamada Y., Akiyama S. The activity and expression of thymidine phosphorylase in human solid tumours. Eur J Cancer. 1996 Jun;32A(7):1227–1232. doi: 10.1016/0959-8049(96)00061-5. [DOI] [PubMed] [Google Scholar]
  23. Tanigawa N., Amaya H., Matsumura M., Katoh Y., Kitaoka A., Aotake T., Shimomatsuya T., Rosenwasser O. A., Iki M. Tumor angiogenesis and expression of thymidine phosphorylase/platelet derived endothelial cell growth factor in human gastric carcinoma. Cancer Lett. 1996 Nov 29;108(2):281–290. doi: 10.1016/s0304-3835(96)04482-5. [DOI] [PubMed] [Google Scholar]
  24. Weber G. Biochemical strategy of cancer cells and the design of chemotherapy: G. H. A. Clowes Memorial Lecture. Cancer Res. 1983 Aug;43(8):3466–3492. [PubMed] [Google Scholar]

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