• 1.上海交通大學(xué)醫(yī)學(xué)院附屬第三人民醫(yī)院普外科(上海 201900);;
  • 2.上海交通大學(xué)醫(yī)學(xué)院附屬第三人民醫(yī)院病理科(上海 201900);

目的  研究轉(zhuǎn)錄因子e2f-1在胃癌發(fā)展過程中不同階段的表達(dá)情況及其臨床意義，判斷其在胃癌發(fā)展中的作用。方法  采用SABC免疫組化法檢測(cè)121例胃癌原發(fā)灶中e2f-1的表達(dá)情況，分析其與臨床病理特征和預(yù)后的關(guān)系。結(jié)果  121例患者e2f-1的表達(dá)陽性率為38.8%（47/121）。隨著胃癌的進(jìn)展，TNMⅠ～Ⅳ期e2f-1表達(dá)陽性率呈逐漸下降的趨勢(shì)(r=－0.320，P lt;0.05)： Ⅰa期62.5%（10/16），Ⅰb期47.1%（8/17），Ⅱ期55.0%（11/20），Ⅲa期40.0%（8/20），Ⅲb期27.3%（6/22），Ⅳ期15.4%（4/26）; 同時(shí)e2f-1的表達(dá)與腫瘤最大直徑、浸潤深度、淋巴結(jié)轉(zhuǎn)移率和累及淋巴站亦呈負(fù)相關(guān)（P lt;0.05）。多參數(shù)檢驗(yàn)分析顯示組織學(xué)類型及生存期是e2f-1陽性表達(dá)的獨(dú)立相關(guān)因素（P lt;0.05）。Log-Rank檢驗(yàn)提示與術(shù)后生存相關(guān)的因素包括累及淋巴站、腫瘤最大直徑、腫瘤位置、淋巴結(jié)轉(zhuǎn)移率、浸潤深度及TNM分期（P lt;0.05）。多因素Cox逐步回歸分析提示累及淋巴站越遠(yuǎn)、e2f-1表達(dá)陽性率越高，則生存期越短（P lt;0.05）。TNM各期中： Ⅰ、Ⅱ期患者e2f-1的陽性高表達(dá)率與更短的生存期相關(guān)（r=－0.304，P lt;0.05），而且e2f-1呈陽性表達(dá)者其預(yù)后顯著差于陰性表達(dá)者（χ2=13.437，P lt;0.05）； 而Ⅲ、Ⅳ期患者e2f-1的表達(dá)與生存期之間無統(tǒng)計(jì)學(xué)關(guān)系（P gt;0.05）。結(jié)論  轉(zhuǎn)錄因子e2f-1是體現(xiàn)早期胃癌惡性行為的標(biāo)記之一，表達(dá)陽性的早期患者生存時(shí)間顯著縮短，是有效的預(yù)后判斷因子； 而在晚期胃癌中e2f-1表達(dá)降低，提示可能與其進(jìn)展有關(guān)。

引用本文： 伍宏彪,吳巨鋼,張鵬,倪曉春,張彪,蘇震東,李小強(qiáng),俞繼衛(wèi),姜波健. 胃癌進(jìn)展中轉(zhuǎn)錄因子e2f-1的表達(dá)變化及其意義. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(6): 573-580. doi: 復(fù)制

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1. Mashta O. Stomach cancer incidence has halved over past 30 years in Britain [J]. BMJ, 2009; 339: b3281.
2. Mousavi SM, Somi MH. Gastric cancer in Iran 1966-2006 [J]. Asian Pac J Cancer Prev, 2009; 10(3): 407-412.
3. Li ZX, Kaminishi M. A comparison of gastric cancer between Japan and China [J]. Gastric Cancer, 2009; 12(1): 52-53.
4. 季加孚. 胃癌外科的發(fā)展趨勢(shì) [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(1): 1-3.
5. 朱正綱. 胃癌外科治療相關(guān)問題的基本認(rèn)識(shí) [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15 (1): 1-3.
6. Cunningham D, Jost LM, Purkalne G, et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of gastric cancer [J]. Ann Oncol, 2005; 16 Suppl 1: i22-i23.
7. Inoue M, Tsugane S. Epidemiology of gastric cancer in Japan [J]. Postgrad Med J, 2005; 81(957): 419-424.
8. Seifried LA, Talluri S, Cecchini M, et al. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption [J]. J Virol, 2008; 82(9): 4511-4520.
9. Findlay GM, Pawson T. How is SOS activated? Let us count the ways [J]. Nat Struct Mol Biol, 2008; 15(6): 538-540.
10. Boykevisch S, Zhao C, Sondermann H, et al. Regulation of ras signaling dynamics by Sos-mediated positive feedback [J]. Curr Biol, 2006; 16(21): 2173-2179.
11. Hinrichsen R, Hansen AH, Hauns S, et al. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy [J]. Cell Prolif, 2008; 41(5): 813-829.
12. Ogino A, Yoshino A, Katayama Y, et al. The p15(INK4b)/p16(INK4a)/RB1 pathway is frequently deregulated in human pituitary adenomas [J]. J Neuropathol Exp Neurol, 2005; 64(5): 398-403.
13. Valeyev NV, Heslop-Harrison P, Postlethwaite I, et al. Cr-osstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels [J]. Mol Biosyst, 2009; 5(1): 43-51.
14. Seavilleklein G, Amer N, Evagelidis A, et al. PKC phosphorylation modulates PKA-dependent binding of the R domain to other domains of CFTR [J]. Am J Physiol Cell Physiol, 2008; 295(5): C1366-C1375.
15. Sterin-Borda L, Bernabeo G, Ganzinelli S, et al. Role of nitric oxide/cyclic GMP and cyclic AMP in beta3 adrenoceptor-chronotropic response [J]. J Mol Cell Cardiol, 2006; 40(4): 580-588.
16. Stites EC, Trampont PC, Ma Z, et al. Network analysis of oncogenic Ras activation in cancer [J]. Science, 2007; 318(5849): 463-467.
17. Wu Z, Zheng S, Yu Q. The E2F family and the role of E2F1 in apoptosis [J]. Int J Biochem Cell Biol, 2009; 41(12): 2389-2397.
18. Schayek H, Bentov I, Rotem I, et al. Transcription factor E2F1 is a potent transactivator of the insulin-like growth factor-Ⅰ receptor (IGF-ⅠR) gene [J]. Growth Horm IGF Res, 2010; 20(1): 68-72.
19. Lee KH, Chen YL, Yeh SD, et al. MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation [J]. Oncogene, 2009; 28(38): 3360-3370.
20. Huang CL, Liu D, Nakano J, et al. E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer [J]. Clin Cancer Res, 2007; 13(23): 6938-6946.
21. Cassimere EK, Pyndiah S, Sakamuro D. The c-MYC-interacting proapoptotic tumor suppressor BIN1 is a transcriptional target for E2F1 in response to DNA damage [J]. Cell Death Differ, 2009; 16(12): 1641-1653.
22. Jenal M, Trinh E, Britschgi C, et al. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1 [J]. Mol Cancer Res, 2009; 7(6): 916-922.
23. Worku D, Jouhra F, Jiang GW, et al. Evidence of a tumour suppressive function of E2F1 gene in human breast cancer [J]. Anticancer Res, 2008; 28(4B): 2135-2139.
24. Ozaki T, Okoshi R, Ono S, et al. Deregulated expression of E2F1 promotes proteolytic degradation of tumor suppressor p73 and inhibits its transcriptional activity [J]. Biochem Biophys Res Commun, 2009; 387(1): 143-148.
25. Liontos M, Niforou K, Velimezi G, et al. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas [J]. Am J Pathol, 2009; 175(1): 376-391.
26. Alonso MM, Alemany R, Fueyo J, et al. E2F1 in gliomas: a paradigm of oncogene addiction [J]. Cancer Lett, 2008; 263(2): 157-163.
27. Yu JW, Wu JG, Zheng LH, et al. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma [J]. J Exp Clin Cancer Res, 2009; 28: 55.
28. Suzuki T, Yasui W, Yokozaki H, et al. Expression of the E2F family in human gastrointestinal carcinomas [J]. Int J Cancer, 1999; 81(4): 535-538.
29. Jamshidi-Parsian A, Dong Y, Zheng X, et al. Gene expression profiling of E2F-1-induced apoptosis [J]. Gene, 2005; 344: 67-77.
30. Xie Y, Wang C, Li L, et al. Overexpression of E2F-1 inhibits progression of gastric cancer in vitro [J]. Cell Biol Int, 2009; 33(6): 640-649.
  1. 1. Mashta O. Stomach cancer incidence has halved over past 30 years in Britain [J]. BMJ, 2009; 339: b3281.
  2. 2. Mousavi SM, Somi MH. Gastric cancer in Iran 1966-2006 [J]. Asian Pac J Cancer Prev, 2009; 10(3): 407-412.
  3. 3. Li ZX, Kaminishi M. A comparison of gastric cancer between Japan and China [J]. Gastric Cancer, 2009; 12(1): 52-53.
  4. 4. 季加孚. 胃癌外科的發(fā)展趨勢(shì) [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(1): 1-3.
  5. 5. 朱正綱. 胃癌外科治療相關(guān)問題的基本認(rèn)識(shí) [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15 (1): 1-3.
  6. 6. Cunningham D, Jost LM, Purkalne G, et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of gastric cancer [J]. Ann Oncol, 2005; 16 Suppl 1: i22-i23.
  7. 7. Inoue M, Tsugane S. Epidemiology of gastric cancer in Japan [J]. Postgrad Med J, 2005; 81(957): 419-424.
  8. 8. Seifried LA, Talluri S, Cecchini M, et al. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption [J]. J Virol, 2008; 82(9): 4511-4520.
  9. 9. Findlay GM, Pawson T. How is SOS activated? Let us count the ways [J]. Nat Struct Mol Biol, 2008; 15(6): 538-540.
  10. 10. Boykevisch S, Zhao C, Sondermann H, et al. Regulation of ras signaling dynamics by Sos-mediated positive feedback [J]. Curr Biol, 2006; 16(21): 2173-2179.
  11. 11. Hinrichsen R, Hansen AH, Hauns S, et al. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy [J]. Cell Prolif, 2008; 41(5): 813-829.
  12. 12. Ogino A, Yoshino A, Katayama Y, et al. The p15(INK4b)/p16(INK4a)/RB1 pathway is frequently deregulated in human pituitary adenomas [J]. J Neuropathol Exp Neurol, 2005; 64(5): 398-403.
  13. 13. Valeyev NV, Heslop-Harrison P, Postlethwaite I, et al. Cr-osstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels [J]. Mol Biosyst, 2009; 5(1): 43-51.
  14. 14. Seavilleklein G, Amer N, Evagelidis A, et al. PKC phosphorylation modulates PKA-dependent binding of the R domain to other domains of CFTR [J]. Am J Physiol Cell Physiol, 2008; 295(5): C1366-C1375.
  15. 15. Sterin-Borda L, Bernabeo G, Ganzinelli S, et al. Role of nitric oxide/cyclic GMP and cyclic AMP in beta3 adrenoceptor-chronotropic response [J]. J Mol Cell Cardiol, 2006; 40(4): 580-588.
  16. 16. Stites EC, Trampont PC, Ma Z, et al. Network analysis of oncogenic Ras activation in cancer [J]. Science, 2007; 318(5849): 463-467.
  17. 17. Wu Z, Zheng S, Yu Q. The E2F family and the role of E2F1 in apoptosis [J]. Int J Biochem Cell Biol, 2009; 41(12): 2389-2397.
  18. 18. Schayek H, Bentov I, Rotem I, et al. Transcription factor E2F1 is a potent transactivator of the insulin-like growth factor-Ⅰ receptor (IGF-ⅠR) gene [J]. Growth Horm IGF Res, 2010; 20(1): 68-72.
  19. 19. Lee KH, Chen YL, Yeh SD, et al. MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation [J]. Oncogene, 2009; 28(38): 3360-3370.
  20. 20. Huang CL, Liu D, Nakano J, et al. E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer [J]. Clin Cancer Res, 2007; 13(23): 6938-6946.
  21. 21. Cassimere EK, Pyndiah S, Sakamuro D. The c-MYC-interacting proapoptotic tumor suppressor BIN1 is a transcriptional target for E2F1 in response to DNA damage [J]. Cell Death Differ, 2009; 16(12): 1641-1653.
  22. 22. Jenal M, Trinh E, Britschgi C, et al. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1 [J]. Mol Cancer Res, 2009; 7(6): 916-922.
  23. 23. Worku D, Jouhra F, Jiang GW, et al. Evidence of a tumour suppressive function of E2F1 gene in human breast cancer [J]. Anticancer Res, 2008; 28(4B): 2135-2139.
  24. 24. Ozaki T, Okoshi R, Ono S, et al. Deregulated expression of E2F1 promotes proteolytic degradation of tumor suppressor p73 and inhibits its transcriptional activity [J]. Biochem Biophys Res Commun, 2009; 387(1): 143-148.
  25. 25. Liontos M, Niforou K, Velimezi G, et al. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas [J]. Am J Pathol, 2009; 175(1): 376-391.
  26. 26. Alonso MM, Alemany R, Fueyo J, et al. E2F1 in gliomas: a paradigm of oncogene addiction [J]. Cancer Lett, 2008; 263(2): 157-163.
  27. 27. Yu JW, Wu JG, Zheng LH, et al. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma [J]. J Exp Clin Cancer Res, 2009; 28: 55.
  28. 28. Suzuki T, Yasui W, Yokozaki H, et al. Expression of the E2F family in human gastrointestinal carcinomas [J]. Int J Cancer, 1999; 81(4): 535-538.
  29. 29. Jamshidi-Parsian A, Dong Y, Zheng X, et al. Gene expression profiling of E2F-1-induced apoptosis [J]. Gene, 2005; 344: 67-77.
  30. 30. Xie Y, Wang C, Li L, et al. Overexpression of E2F-1 inhibits progression of gastric cancer in vitro [J]. Cell Biol Int, 2009; 33(6): 640-649.