Clinical significance of Ankyrin repeat domain 12 expression in colorectal cancer

Journal of Experimental & Clinical Cancer Research

Shu Zheng³  Weiting Ge³  Xuefeng Fang²  Zhong Shi³  Dan Li³  Rui Bai¹ 

[1] Department of Medical Oncology, Hangzhou First People’s Hospital, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China;Department of Medical Oncology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China;Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang, China

关键词: Prognostic factor;    Metastasis;    Colorectal cancer;    Ankyrin repeat domain 12 (ANKRD12);   

Others  :  824989
DOI  :  10.1186/1756-9966-32-35

 received in 2013-04-11, accepted in 2013-05-14,  发布年份 2013

【 摘 要 】

Background

Ankyrin repeat domain 12 (ANKRD12), is encoding a 224 kDa nuclear protein and most conserved at its N-terminal ankyrin repeats region and the C-terminal co-activator interacting domain. The aim of this study was to investigate the ANKRD12 mRNA expression in colorectal cancer (CRC) tumor tissues and the normal adjacent mucosa and its potential relevance to clinicopathological characteristics and prognosis.

Methods

Surgical specimens of tumor tissues (n = 68) and adjacent normal mucosa (n = 51) were obtained from CRC patients. The ANKRD12 mRNA expression was measured by quantitative real time reverse transcriptase polymerase chain reaction. The relationship between ANKRD12 mRNA expression and clinicopathological features was analyzed by appropriate statistics. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between ANKRD12 expression and prognosis of CRC patients.

Results

The relative mRNA expression of ANKRD12 were significantly lower in CRC tumor tissues than in the normal adjacent mucosa (P < 0.001), and the cases with low ANKRD12 expression showed a higher frequency of liver metastasis (P = 0.015). Kaplan–Meier analysis indicated that patients (CRC without liver metastasis) with low ANKRD12 expression had poor overall survival (P = 0.041). Multivariate analysis showed that low ANKRD12 expression was an independent predictor of overall survival.

Conclusion

This study revealed that ANKRD12 mRNA were down regulated in CRC tumor tissues and low ANKRD12 expression was correlated with liver metastasis and poor survival of CRC patients.

【 授权许可】

   
2013 Bai et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Siegel R, Naishadham D, Jemal A: Cancer statistics. CA Cancer J Clin 2012, 62:10-29.
• [2]Zhang A, Yeung PL, Li CW, Tsai SC, Dinh GK, Wu X, Li H, Chen JD: Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators. J Biol Chem 2004, 279:33799-33805.
• [3]Zhang A, Li CW, Tsai SC, Chen JD: Subcellular localization of ankyrin repeats cofactor-1 regulates its corepressor activity. J Cell Biochem 2007, 101:1301-1315.
• [4]Zhang A, Li CW, Chen JD: Characterization of transcriptional regulatory domains of ankyrin repeat cofactor-1. Biochem Biophys Res Commun 2007, 358:1034-1040.
• [5]Bork P: Hundreds of ankyrin-like repeats in functionally diverse proteins: mobile modules that cross phyla horizontally? Proteins 1993, 17:363-374.
• [6]Sedgwick SG, Smerdon SJ: The ankyrin repeat: a diversity of interactions on a common structural framework. Trends Biochem Sci 1999, 24:311-316.
• [7]Li CW, Dinh GK, Zhang A, Chen JD: Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function. Biochem J 2008, 413:349-357.
• [8]Behrends U, Schneider I, Rossler S, Frauenknecht H, Golbeck A, Lechner B, Eigenstetter G, Zobywalski C, Muller-Weihrich S, Graubner U: Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries. Int J Cancer 2003, 106:244-251.
• [9]Powell JA, Gardner AE, Bais AJ, Hinze SJ, Baker E, Whitmore S, Crawford J, Kochetkova M, Spendlove HE, Doggett NA: Sequencing, transcript identification, and quantitative gene expression profiling in the breast cancer loss of heterozygosity region 16q24.3 reveal three potential tumor-suppressor genes. Genomics 2002, 80:303-310.
• [10]Neilsen PM, Cheney KM, Li CW, Chen JD, Cawrse JE, Schulz RB, Powell JA, Kumar R, Callen DF: Identification of ANKRD11 as a p53 coactivator. J Cell Sci 2008, 121:3541-3552.
• [11]Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM: The nuclear receptor superfamily: the second decade. Cell 1995, 83:835-839.
• [12]Bourguet W, Ruff M, Chambon P, Gronemeyer H, Moras D: Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-alpha. Nature 1995, 375:377-382.
• [13]Bannister AJ, Kouzarides T: The CBP co-activator is a histone acetyltransferase. Nature 1996, 384:641-643.
• [14]Ogryzko VV, Kotani T, Zhang X, Schiltz RL, Howard T, Yang XJ, Howard BH, Qin J, Nakatani Y: Histone-like TAFs within the PCAF histone acetylase complex. Cell 1998, 94:35-44.
• [15]Wang T, Kobayashi T, Takimoto R, Denes AE, Snyder EL, Brachmann RK, el-Deiry WS: hADA3 is required for p53 activity. EMBO J 2001, 20:6404-6413.
• [16]Kumar A, Zhao Y, Meng G, Zeng M, Srinivasan S, Delmolino LM, Gao Q, Dimri G, Weber GF, Wazer DE: Human papillomavirus oncoprotein E6 inactivates the transcriptional coactivator human ADA3. Mol Cell Biol 2002, 22:5801-5812.
• [17]Zeng M, Kumar A, Meng G, Gao Q, Dimri G, Wazer D, Band H, Band V: Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator. J Biol Chem 2002, 277:45611-45618.
• [18]Nag A, Germaniuk-Kurowska A, Dimri M, Sassack MA, Gurumurthy CB, Gao Q, Dimri G, Band H, Band V: An essential role of human Ada3 in p53 acetylation. J Biol Chem 2007, 282:8812-8820.
• [19]Hollstein M, Sidransky D, Vogelstein B, Harris CC: p53 mutations in human cancers. Science 1991, 253:49-53.
• [20]Hollstein M, Rice K, Greenblatt MS, Soussi T, Fuchs R, Sorlie T, Hovig E, Smith-Sorensen B, Montesano R, Harris CC: Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res 1994, 22:3551-3555.
• [21]Lane DP: Cancer. p53, guardian of the genome. Nature 1992, 358:15-16.