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Expression of survivin protein in colorectal adenocarcinoma
Jun Xiao, Chang-Sheng Deng, You-Qing Zhu
Jun Xiao, Chang-Sheng Deng, You-Qing Zhu, Digestive Department.Zhongnan Hospital of Wuhan University, 39 Dong-hu Road, Wuhan 430071, Hubei Province, China
Correspondence to: Prof. Chang-Sheng Deng, Digestive Department, Zhongnan Hospital of Wuhan University, 39 Donghu Road, Wuhan 430071, Hubei Province, China. email@example.com
Received: August 10, 2002 Revised: August 20, 2002 Accepted: August 29, 2002 Published online: May 15, 2003
To investigate the expression of survivin and its relationship with proliferation and apoptosis in colorectal adenoma and adenocarcinoma.
Using terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and immunohistochemistry S-P method, the authors examined the expression of survivin, Ki-67 and apoptotic cell in situ in 60 cases of colorectal adenocarcinoma, 35 adenoma and 20 normal colonic mucosa.
Survivin expression was observed in 36 of 60 (60.0%) cases of colorectal adenocarcinoma and in 6 of 35 (17.1%) cases of adenoma. In contrast, normal colonic mucosa did not express survivin. Overexpression of survivin was related to the differentiation grade of colorectal adenocarcinoma,however there was no correlation with Dukes'sstage of lymph node metastasis. Ki-67 labeling index (LI) was higher in colorectal adenocarcinoma than that in adenoma (39.1±10.4% vs 22.3±6.2%, P<0.01). The apoptosis index (AI) of colorectal adenocarcinoma and adenoma was significantly higher than that of normal tissues (P<0.01). More apoptotic cells were noticed in well and moderate differentiated adenocarcinoma than those in poorly differentiated adenocarcinoma (P<0.05). Survivin positive adenoma and adenocarcinoma had significantly lower values for AI than survivin negative tumors (P<0.01), and the Ki-67 LI in survivin positive adenoma and adenocarcinoma were higher than that in survivin negative tumors (P<0.01).
Up-regulation of survivin expression in adenocarcinoma suggests that survivin may play an important role in human colorectal tumorigenesis through the inhibition of apoptosis and acceleration of proliferative activity. Survivin may be a new prognostic implication in colorectal adenocarcinoma and serve as a widely applicable target for anticancer gene therapy.
Key Words: N/A
Citation: Xiao J, Deng CS, Zhu YQ. Expression of survivin protein in colorectal adenocarcinoma. Shijie Huaren Xiaohua Zazhi 2003; 11(5): 540-543
本研究显示Survivin蛋白在大肠腺癌高、中、低分化组中的表达率分别为45.5%, 52.2%和73.1%, 3组间差异有显著性(P<0.05), 提示Survivin蛋白的表达率在一定程度上反映了腺癌的恶性程度, 可以作为预后不良参数指标. Rodel et al报道直肠癌高Survivin表达的患者5 a生存率明显低于低Survivin表达者(18% vs 77%), 肿瘤转移前者是后者的4倍(78% vs 18%), 认为Survivin阳性表达是直肠癌转移的高危因素. 亦有文献报道Survivin检测能预测Ⅱ期结肠癌的发生, 因而我们认为检测Survivin对预测肿瘤的发生, 发展和预后提供了一新的指标. 我们还发现尽管Survivin在大肠腺癌中有过表达, 但与Dukes'分期和淋巴结转移无明显关系, 与国内学者在肺癌、子宫颈癌等研究结果一致[33,34]. 这提示在大肠癌进展过程中还受其他癌基因的调控, 是多基因参与, 多因素共同作用的结果[35,36], Survivin基因与其他癌基因关系有待进一步研究.
Zhang ZS, Zhang YL. Progress in research of colorectal cancer in China.ShijieHuarenXiaohuaZazhi. 2001;9:489-494.
Li SR. Early diagnosis of colorectal cancer.ShijieHuarenXiaohuaZazhi. 2001;9:780-782.
Liu LN. Cell apoptosis and colorectal cancer.ShijieHuarenXiaohuaZazhi. 2002;10:422-423.
Song JD, Gao F, Jiang LY, Zhao X, Chen YH, Wang YQ. Molecular mechanism of cell apoptosis.ShijieHuarenXiaohuaZazhi. 2002;10:429-431.
Huang PL, Zhu SN, Lu SL, Dai SZ, Jin YL. Inhibitor of fatty acid synthase induced apoptosis in human colonic cancer cells.World J Gastroenterol. 2000;6:295-297.
Peng ZH, Xing TH, Qiu GQ, Tang HM. Relationship between Fas/FasL expression and apoptosis of colon adenocarcinoma cell lines.World J Gastroenterol. 2001;7:88-92.
Zhang GY, Yuan WJ, He CM. Study of inhibit the proliferation and induce apoptosis of human colon adenocarcinoma cell line HCT116.World J Gastroenterol. 2000;6:85.
Hu JY, Wang S, Zhu JG, Zhou GH, Sun QB. Expression of B7 costimulation molecules by colorectal cancer cells reduces tumorigenicity and induces anti-tumor immunity.World J Gastroenterol. 1999;5:147-151.
Qian WF, Huang ZH, Chi DB. Herpes simplex virus thymidine kinase/ganciclovir system combined with 5-FU for the treatment of experimental colorectal cancer.ShijieHuarenXiaohuaZazhi. 2001;9:190-193.
Huang ZH, Qian WF, Chi DB, Jiang ZS. Apoptosis in human colorectal cancer LoVo cells induced by HSVtk/GCV system in vitro.ShijieHuarenXiaohuaZazhi. 2001;9:194-197.
Lu XP, Li BJ, Chen SL, Lu B, Jiang NY. Effect of chemotherapy or targeting chemotherapy on apoptosis of colorectal carcinoma.ShijieHuarenXiaohuaZazhi. 1999;7:332-334.
Wang LS, Pan LJ, Chen CL, Li MS, Shun Y, Zhang YL, Zhou DY. Effect of Bifidobacterium on proliferation and apoptosis of experimental large bowel carcinoma in situ.ShijieHuarenXiaohuaZazhi. 2000;8:429-431.
Yu LL, Yu JP, Ran ZX, Yu HG. Relationship between nuclear factor-kappa B, apoptosis and proliferation in colorectal neoplasia.ShijieHuarenXiaohuaZazhi. 2002;10:309-312.
Ikeguchi M, Ueta T, Yamane Y, Hirooka Y, Kaibara N. Inducible nitric oxide synthase and survivin messenger RNA expression in hepatocellular carcinoma.Clin Cancer Res. 2002;8:3131-3136.
Ikeguchi M, Kaibara N. Survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma.Br J Cancer. 2002;87:883-887.
Nasu S, Yagihashi A, Izawa A, Saito K, Asanuma K, Nakamura M, Kobayashi D, Okazaki M, Watanabe N. Survivin mRNA expression in patients with breast cancer.Anticancer Res. 2002;22:1839-1843.
Sui L, Dong Y, Ohno M, Watanabe Y, Sugimoto K, Tokuda M. Survivin expression and its correlation with cell proliferation and prognosis in epithelial ovarian tumors.Int J Oncol. 2002;21:315-320.
Das A, Tan WL, Teo J, Smith DR. Expression of survivin in primary glioblastomas. J Cancer Res.Clin Oncol. 2002;128:302-306.
Ikeguchi M, Ueda T, Sakatani T, Hirooka Y, Kaibara N. Expression of survivin messenger RNA correlates with poor prognosis in patients with hepatocellular carcinoma.Diagn Mol Pathol. 2002;11:33-40.
Yu J, Leung WK, Ebert MP, Ng EK, Go MY, Wang HB, Chung SC, Malfertheiner P, Sung JJ. Increased expression of survivin in gastric cancer patients and in first degree relatives.Br J Cancer. 2002;87:91-97.
Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer.Cancer Res. 1998;58:5071-5074.
Altieri DC. The molecular basis and potential role of survivin in cancer diagnosis and therapy.Trends Mol Med. 2001;7:542-547.
Conway EM, Pollefeyt S, Steiner-Mosonyi M, Luo W, Devriese A, Lupu F, Bono F, Leducq N, Dol F, Schaeffer P. Deficiency of survivin in transgenic mice exacerbates Fas-induced apoptosis via mitochondrial pathways.Gastroenterology. 2002;123:619-631.
Azuhata T, Scott D, Takamizawa S, Wen J, Davidoff A, Fukuzawa M, Sandler A. The inhibitor of apoptosis protein survivin is associated with high-risk behavior of neuroblastoma.J PediatrSurg. 2001;36:1785-1791.
Lin M, Meng X, Cai Z, Ye X. Expression and clinical significance of anti-apoptosis gene, survivin, in acute leukemia.ZhonghuaXueYexueZazhi. 2002;23:251-253.
Ikeguchi M, Liu J, KaibaraN . Expression of survivin mRNA and protein in gastric cancer cell line (MKN-45) during cisplatin treatment.Apoptosis. 2002;7:23-29.
Kawasaki H, Toyoda M, Shinohara H, Okuda J, Watanabe I, Yamamoto T, Tanaka K, Tenjo T, Tanigawa N. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis.Cancer. 2001;91:2026-2032.
Andersen MH, Pedersen LO, Capeller B, Brocker EB, Becker JC, Thor StratenP. Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients.Cancer Res. 2001;61:5964-5968.
Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC. Control of apoptosis and mitotic spindle checkpoint by survivin.Nature. 1998;396:580-584.
Giodini A, Kallio MJ, Wall NR, Gorbsky GJ, Tognin S, Marchisio PC, Symons M, Altieri DC. Regulation of microtubule stability and mitotic progression by survivin.Cancer Res. 2002;62:2462-2467.
Rodel F, Hoffmann J, Grabenbauer GG, Papadopoulos T, Weiss C, Gunther K, Schick C, Sauer R, Rodel C. High survivin expression is associated with reduced apoptosis in rectal cancer and may predict disease-free survival after preoperative radiochemotherapy and surgical resection.StrahlentherOnkol. 2002;178:426-435.
Wang X, Chen S, Zhang Z. Expression of surviving gene and its relationship with expression of P53, c-myc, k-ras proteins in non-small-cell lung cancer.ZhonghuaJiehe He HuxiZazhi. 2001;24:371-374.
Wang M, Wang B, Wang X. A novel antiapoptosis gene, survivin, bcl-2, p53 expression in cervical carcinomas.ZhonghuaFuchankeZazhi. 2001;36:546-548.
Mirza A, McGuirk M, Hockenberry TN, Wu Q, Ashar H, Black S, Wen SF, Wang L, Kirschmeier P, Bishop WR. Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway.Oncogene. 2002;21:2613-2622.
Zhang T, Otevrel T, Gao Z, Ehrlich SM, Fields JZ, Boman BM. Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer.Cancer Res. 2001;61:8664-8667.