Livin expression is an independent factor in rectal cancer patients with or without preoperative radiotherapy

Radiation Oncology

Xiao-Feng Sun¹  Birgit Olsson¹  Gunnar Adell²  Hong Zhang⁴  Zhen-Yu Ding³ 

[1] Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Country Council of Östergötland, University of Linköping, Linköping, Sweden;Department of Oncology, Karolinska University Hospital, Stockholm, Sweden;Department of Thoracic Oncology, Cancer Center, and the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China;School of Medicine, Örebro University, SE 701 82 Örebro, Sweden

关键词: Radiotherapy;    Livin;    Rectal cancer;   

Others  :  829557
DOI  :  10.1186/1748-717X-8-281

 received in 2013-07-07, accepted in 2013-11-17,  发布年份 2013

【 摘 要 】

Background

This study was aimed to investigate the expression significance of Livin in relation to radiotherapy (RT), clinicopathological and biological factors of rectal cancer patients.

Methods

This study included 144 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative radiotherapy. Tissue microarray samples from the excised primary rectal cancers, normal mucosa and lymph node metastases were immunostained with Livin antibody. The proliferation of colon cancer cell lines SW620 and RKO was assayed after Livin knock-down.

Results

The expression of Livin was significantly increased from adjacent (P = 0.051) or distant (P = 0.028) normal mucosa to primary tumors. 15.4% (2/13) and 39.7% (52/131) patients with Livin-negative and positive tumors died at 180 months after surgery, and the difference tended to be statistically significant (P = 0.091). In multivariate analyses, the difference achieved statistical significance, independent of TNM stage, local and distant recurrence, grade of differentiation, gender, and age (odds ratio = 5.09, 95% CI: 1.01-25.64, P = 0.048). The in vitro study indicated colon cancer cells with Livin knock-down exhibited decreased proliferation compared with controls after RT.

Conclusions

The expression of Livin was was independently related to survival in rectal cancer patients, suggesting Livin as a useful prognostic factor for rectal cancer patients.

【 授权许可】

   
2013 Ding et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Canc J Clin 2010, 60:277-300.
• [2]Meza R, Jeon J, Renehan AG, Luebeck EG: Colorectal cancer incidence trends in the United States and United kingdom: evidence of right- to left-sided biological gradients with implications for screening. Canc Res 2010, 70:5419-5429.
• [3]Trial SRC: Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997, 336:980-987.
• [4]Camma C, Giunta M, Fiorica F, Pagliaro L, Craxi A, Cottone M: Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA 2000, 284:1008-1015.
• [5]Van Den Brink M, Van Den Hout WB, Stiggelbout AM, et al.: Cost-utility analysis of preoperative radiotherapy in patients with rectal cancer undergoing total mesorectal excision: a study of the Dutch Colorectal Cancer Group. J Clin Oncol 2004, 22:244-253.
• [6]Knutsen A, Adell G, Sun XF: Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy. Int J Radiat Oncol Biol Phys 2004, 60:149-155.
• [7]Lin JH, Deng G, Huang Q, Morser J: KIAP, a novel member of the inhibitor of apoptosis protein family. Biochem Biophys Res Commun 2000, 279:820-831.
• [8]Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS, Dixit VM: ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol 2000, 10:1359-1366.
• [9]Kasof GM, Gomes BC: Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem 2001, 276:3238-3246.
• [10]Tanabe H, Yagihashi A, Tsuji N, Shijubo Y, Abe S, Watanabe N: Expression of survivin mRNA and livin mRNA in non-small-cell lung cancer. Lung Canc 2004, 46:299-304.
• [11]Gazzaniga P, Gradilone A, Giuliani L, et al.: Expression and prognostic significance of LIVIN, SURVIVIN and other apoptosis-related genes in the progression of superficial bladder cancer. Ann Oncol 2003, 14:85-90.
• [12]Choi J, Hwang YK, Sung KW, et al.: Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia. Blood 2007, 109:471-477.
• [13]Xiang Y, Yao H, Wang S, et al.: Prognostic value of Survivin and Livin in nasopharyngeal carcinoma. Laryngoscope 2006, 116:126-130.
• [14]Ashhab Y, Alian A, Polliack A, Panet A, Ben Yehuda D: Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern. FEBS Lett 2001, 495:56-60.
• [15]Takeuchi H, Kim J, Fujimoto A, et al.: X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling. Clin Canc Res 2005, 11:7621-7628.
• [16]Adell G, Zhang H, Jansson A, Sun XF, Stal O, Nordenskjold B: Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer. Int J Radiat Oncol Biol Phys 2001, 50:659-663.
• [17]Adell G, Sun XF, Stal O, Klintenberg C, Sjodahl R, Nordenskjold B: p53 status: an indicator for the effect of preoperative radiotherapy of rectal cancer. Radiother Oncol 1999, 51:169-174.
• [18]Loftas P, Onnesjo S, Widegren E, et al.: Expression of FXYD-3 is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy. Int J Radiat Oncol Biol Phys 2009, 75:137-142.
• [19]Arlehag L, Adell G, Knutsen A, Thorstenson S, Sun XF: ATM expression in rectal cancers with or without preoperative radiotherapy. Oncol Rep 2005, 14:313-317.
• [20]Adell GC, Zhang H, Evertsson S, Sun XF, Stal OH, Nordenskjold BA: Apoptosis in rectal carcinoma: prognosis and recurrence after preoperative radiotherapy. Cancer 2001, 91:1870-1875.
• [21]Yang L, Cao Z, Yan H, Wood WC: Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy. Canc Res 2003, 63:6815-6824.
• [22]Wang R, Lin F, Wang X, et al.: Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells. Canc Gene Ther 2008, 15:402-412.
• [23]Slagsvold JE, Pettersen CH, Storvold GL, Follestad T, Krokan HE, Schonberg SA: DHA alters expression of target proteins of cancer therapy in chemotherapy resistant SW620 colon cancer cells. Nutr Canc 2010, 62:611-621.
• [24]Yagihashi A, Ohmura T, Asanuma K, et al.: Detection of autoantibodies to survivin and livin in sera from patients with breast cancer. Clin Chim Acta 2005, 362:125-130.
• [25]Ding ZY, Liu GH, Birgit O, Sun XF: Upregulation of the antiapoptotic factor Livin contributes to cisplatin resistance in colon cancer cells. Tumor Biol 2013, 34:683-693.
• [26]Kim DK, Alvarado CS, Abramowsky CR, et al.: Expression of inhibitor-of-apoptosis protein (IAP) livin by neuroblastoma cells: correlation with prognostic factors and outcome. Pediatr Dev Pathol 2005, 8:621-629.
• [27]Nedelcu T, Kubista B, Koller A, et al.: Livin and Bcl-2 expression in high-grade osteosarcoma. J Canc Res Clin Oncol 2008, 134:237-244.
• [28]Yuan D, Liu L, Gu D: Transcriptional regulation of livin by beta-catenin/TCF signaling in human lung cancer cell lines. Mol Cell Biochem 2007, 306:171-178.
• [29]Yan B, Kong M, Chen S, Chen YH: VEGF stimulation enhances Livin protein synthesis through mTOR signaling. J Cell Biochem 2010, 111:1114-1124.
• [30]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
• [31]Chang H, Schimmer AD: Livin/melanoma inhibitor of apoptosis protein as a potential therapeutic target for the treatment of malignancy. Mol CancTher 2007, 6:24-30. BioMed Central Full Text
• [32]Luo J, Solimini NL, Elledge SJ: Principles of cancer therapy: oncogene and non-oncogene addiction. Cell 2009, 136:823-837.
• [33]Sanna MG, da Silva CJ, Ducrey O, et al.: IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition. Mol Cell Biol 2002, 22:1754-1766.
• [34]Lee JH, Paull TT: Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene 2007, 26:7741-7748.
• [35]Brown JM, Attardi LD: The role of apoptosis in cancer development and treatment response. Nat Rev Canc 2005, 5:231-237.
• [36]Ye L, Song X, Li S, et al.: Livin-alpha promotes cell proliferation by regulating G1-S cell cycle transition in prostate cancer. Prostate 2011, 71:42-51.
• [37]Crnkovic-Mertens I, Hoppe-Seyler F, Butz K: Induction of apoptosis in tumor cells by siRNA-mediated silencing of the livin/ML-IAP/KIAP gene. Oncogene 2003, 22:8330-8336.
• [38]Crnkovic-Mertens I, Semzow J, Hoppe-Seyler F, Butz K: Isoform-specific silencing of the Livin gene by RNA interference defines Livin beta as key mediator of apoptosis inhibition in HeLa cells. J Mol Med (Berl) 2006, 84:232-240.