Skip to main content
Erschienen in: Clinical and Translational Oncology 3/2013

01.03.2013 | Research Article

Decreased expression of chromodomain helicase DNA-binding protein 5 is an unfavorable prognostic marker in patients with primary gallbladder carcinoma

verfasst von: Xilin Du, Tao Wu, Jianguo Lu, Li Zang, Nuan Song, Tao Yang, Huadong Zhao, Shengzhi Wang

Erschienen in: Clinical and Translational Oncology | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Aim

Chromodomain helicase DNA-binding protein 5 (CHD5) plays a role in normal neural development and in tumorigenesis of various human cancers. However, its role in primary gallbladder carcinoma (PGC) is still unclear. The aim of this study was to investigate CHD5 expression in PGC and its clinical significance.

Methods

CHD5 mRNA and protein expression in 120 PGC and 20 normal gallbladder specimens was determined by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) and Western blotting analysis, respectively.

Results

The expression levels of CHD5 mRNA and protein in PGC tissues were both significantly lower than those in the normal epithelium of the gallbladder (mRNA: P = 0.006; protein: P = 0.01). CHD5 mRNA expression was closely correlated with its protein expression (r = 0.8; P < 0.001). Additionally, the low expression of CHD5 protein was significantly associated with high pathologic T stage (P = 0.01) and clinical stage (P = 0.008), and advanced histologic grade (P = 0.009). The expression levels of CHD5 protein in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01). Survival analysis showed that low CHD5 expression was associated with shorter disease-free (P = 0.01) and overall survival (P = 0.008) compared to those with high CHD5 expression in PGC patients. Furthermore, multivariate analyses showed that the decreased expression of CHD5 was an independent prognostic marker for both unfavorable disease-free (P = 0.01) and overall survival (P = 0.006).

Conclusion

CHD5 may be involved in carcinogenesis of PGC and its down-regulation may be significantly correlated with unfavorable clinicopathologic features including poor overall and disease-free survival in patients.
Literatur
1.
Zurück zum Zitat Puhalla H, Wrba F, Kandioler D, Lehnert M, Huynh A, Gruenberger T, Tamandl D, Filipits M (2007) Expression of p21(Wafl/Cip1), p57(Kip2) and HER2/neu in patients with gallbladder cancer. Anticancer Res 27:1679–1684PubMed Puhalla H, Wrba F, Kandioler D, Lehnert M, Huynh A, Gruenberger T, Tamandl D, Filipits M (2007) Expression of p21(Wafl/Cip1), p57(Kip2) and HER2/neu in patients with gallbladder cancer. Anticancer Res 27:1679–1684PubMed
2.
Zurück zum Zitat Roa I, de Aretxabala X, Lantadilla S, Munoz S (2011) ERCC1 (excision repair cross-complementing 1) expression in pT2 gallbladder cancer is a prognostic factor. Histol Histopathol 26:37–43PubMed Roa I, de Aretxabala X, Lantadilla S, Munoz S (2011) ERCC1 (excision repair cross-complementing 1) expression in pT2 gallbladder cancer is a prognostic factor. Histol Histopathol 26:37–43PubMed
3.
Zurück zum Zitat Chen Y, Chen Y, Yu G, Ding H (2011) Lymphangiogenic and angiogentic microvessel density in gallbladder carcinoma. Hepatogastroenterology 58:20–25PubMedCrossRef Chen Y, Chen Y, Yu G, Ding H (2011) Lymphangiogenic and angiogentic microvessel density in gallbladder carcinoma. Hepatogastroenterology 58:20–25PubMedCrossRef
4.
Zurück zum Zitat Misra S, Chaturvedi A, Misra NC (2003) Carcinoma of the gallbladder. Lancet Oncol 4:167–176PubMedCrossRef Misra S, Chaturvedi A, Misra NC (2003) Carcinoma of the gallbladder. Lancet Oncol 4:167–176PubMedCrossRef
5.
Zurück zum Zitat Ando A, Suzuki C (2005) Cooperative function of the CHD5-like protein Mdm39p with a P-type ATPase Spf1p in the maintenance of ER homeostasis in Saccharomyces cerevisiae. Mol Genet Genomics 273:497–506PubMedCrossRef Ando A, Suzuki C (2005) Cooperative function of the CHD5-like protein Mdm39p with a P-type ATPase Spf1p in the maintenance of ER homeostasis in Saccharomyces cerevisiae. Mol Genet Genomics 273:497–506PubMedCrossRef
6.
Zurück zum Zitat Yoshimura S, Yoshimi T, Ohkawa Y, Azuma M, Tachibana T (2010) A rat monoclonal antibody against the chromatin remodeling factor CHD5. Hybridoma (Larchmt) 29:63–66CrossRef Yoshimura S, Yoshimi T, Ohkawa Y, Azuma M, Tachibana T (2010) A rat monoclonal antibody against the chromatin remodeling factor CHD5. Hybridoma (Larchmt) 29:63–66CrossRef
7.
Zurück zum Zitat Potts RC, Zhang P, Wurster AL, Precht P, Mughal MR, Wood WH 3rd, Zhang Y, Becker KG, Mattson MP, Pazin MJ (2011) CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes. PLoS One 6:e24515PubMedCrossRef Potts RC, Zhang P, Wurster AL, Precht P, Mughal MR, Wood WH 3rd, Zhang Y, Becker KG, Mattson MP, Pazin MJ (2011) CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes. PLoS One 6:e24515PubMedCrossRef
8.
Zurück zum Zitat Thompson PM, Gotoh T, Kok M, White PS, Brodeur GM (2003) CHD5, a new member of the chromodomain gene family, is preferentially expressed in the nervous system. Oncogene 22:1002–1011PubMedCrossRef Thompson PM, Gotoh T, Kok M, White PS, Brodeur GM (2003) CHD5, a new member of the chromodomain gene family, is preferentially expressed in the nervous system. Oncogene 22:1002–1011PubMedCrossRef
9.
Zurück zum Zitat Koyama H, Zhuang T, Light JE, Kolla V, Higashi M, McGrady PW, London WB, Brodeur GM (2012) Mechanisms of CHD5 inactivation in neuroblastomas. Clin Cancer Res 18:1588–1597PubMedCrossRef Koyama H, Zhuang T, Light JE, Kolla V, Higashi M, McGrady PW, London WB, Brodeur GM (2012) Mechanisms of CHD5 inactivation in neuroblastomas. Clin Cancer Res 18:1588–1597PubMedCrossRef
10.
Zurück zum Zitat Muthuswamy SK (2009) A new tumor suppressor that regulates tissue architecture. PLoS Med 6:e1000073PubMedCrossRef Muthuswamy SK (2009) A new tumor suppressor that regulates tissue architecture. PLoS Med 6:e1000073PubMedCrossRef
11.
Zurück zum Zitat Law ME, Templeton KL, Kitange G, Smith J, Misra A, Feuerstein BG, Jenkins RB (2005) Molecular cytogenetic analysis of chromosomes 1 and 19 in glioma cell lines. Cancer Genet Cytogenet 160:1–14PubMedCrossRef Law ME, Templeton KL, Kitange G, Smith J, Misra A, Feuerstein BG, Jenkins RB (2005) Molecular cytogenetic analysis of chromosomes 1 and 19 in glioma cell lines. Cancer Genet Cytogenet 160:1–14PubMedCrossRef
12.
Zurück zum Zitat Mokarram P, Kumar K, Brim H, Naghibalhossaini F, Saberi-firoozi M, Nouraie M, Green R, Lee E, Smoot DT, Ashktorab H (2009) Distinct high-profile methylated genes in colorectal cancer. PLoS One 4:e7012PubMedCrossRef Mokarram P, Kumar K, Brim H, Naghibalhossaini F, Saberi-firoozi M, Nouraie M, Green R, Lee E, Smoot DT, Ashktorab H (2009) Distinct high-profile methylated genes in colorectal cancer. PLoS One 4:e7012PubMedCrossRef
13.
Zurück zum Zitat Garcia I, Mayol G, Rodríguez E, Sunol M, Gershon TR, Ríos J, Cheung NK, Kieran MW, George RE, Perez-Atayde AR, Casala C, Galván P, de Torres C, Mora J, Lavarino C (2010) Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma. Mol Cancer 9:277PubMedCrossRef Garcia I, Mayol G, Rodríguez E, Sunol M, Gershon TR, Ríos J, Cheung NK, Kieran MW, George RE, Perez-Atayde AR, Casala C, Galván P, de Torres C, Mora J, Lavarino C (2010) Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma. Mol Cancer 9:277PubMedCrossRef
14.
Zurück zum Zitat Lang J, Tobias ES, Mackie R (2011) Preliminary evidence for involvement of the tumour suppressor gene CHD5 in a family with cutaneous melanoma. Br J Dermatol 164:1010–1016PubMedCrossRef Lang J, Tobias ES, Mackie R (2011) Preliminary evidence for involvement of the tumour suppressor gene CHD5 in a family with cutaneous melanoma. Br J Dermatol 164:1010–1016PubMedCrossRef
15.
Zurück zum Zitat Gorringe KL, Choong DY, Williams LH, Ramakrishna M, Sridhar A, Qiu W, Bearfoot JL, Campbell IG (2008) Mutation and methylation analysis of the chromodomain-helicase-DNA binding 5 gene in ovarian cancer. Neoplasia 10:1253–1258PubMed Gorringe KL, Choong DY, Williams LH, Ramakrishna M, Sridhar A, Qiu W, Bearfoot JL, Campbell IG (2008) Mutation and methylation analysis of the chromodomain-helicase-DNA binding 5 gene in ovarian cancer. Neoplasia 10:1253–1258PubMed
16.
Zurück zum Zitat Mulero-Navarro S, Esteller M (2008) Chromatin remodeling factor CHD5 is silenced by promoter CpG island hypermethylation in human cancer. Epigenetics 3:210–215PubMedCrossRef Mulero-Navarro S, Esteller M (2008) Chromatin remodeling factor CHD5 is silenced by promoter CpG island hypermethylation in human cancer. Epigenetics 3:210–215PubMedCrossRef
17.
Zurück zum Zitat Roh YH, Kim YH, Choi HJ, Lee KE, Roh MS (2008) Syndecan-1 expression in gallbladder cancer and its prognostic significance. Eur Surg Res 41:245–250PubMedCrossRef Roh YH, Kim YH, Choi HJ, Lee KE, Roh MS (2008) Syndecan-1 expression in gallbladder cancer and its prognostic significance. Eur Surg Res 41:245–250PubMedCrossRef
18.
Zurück zum Zitat Alvarez H, Corvalan A, Roa JC, Argani P, Murillo F, Edwards J, Beaty R, Feldmann G, Hong SM, Mullendore M, Roa I, Ibañez L, Pimentel F, Diaz A, Riggins GJ, Maitra A (2008) Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer. Clin Cancer Res 14:2631–2638PubMedCrossRef Alvarez H, Corvalan A, Roa JC, Argani P, Murillo F, Edwards J, Beaty R, Feldmann G, Hong SM, Mullendore M, Roa I, Ibañez L, Pimentel F, Diaz A, Riggins GJ, Maitra A (2008) Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer. Clin Cancer Res 14:2631–2638PubMedCrossRef
19.
Zurück zum Zitat Ng D, Yang XR, Tucker MA, Goldstein AM (2008) Mutation screening of CHD5 in melanoma-prone families linked to 1p36 revealed no deleterious coding or splice site changes. BMC Res Notes 1:86PubMedCrossRef Ng D, Yang XR, Tucker MA, Goldstein AM (2008) Mutation screening of CHD5 in melanoma-prone families linked to 1p36 revealed no deleterious coding or splice site changes. BMC Res Notes 1:86PubMedCrossRef
20.
Zurück zum Zitat White PS, Thompson PM, Gotoh T, Okawa ER, Igarashi J, Kok M, Winter C, Gregory SG, Hogarty MD, Maris JM, Brodeur GM (2005) Definition and characterization of a region of 1p36.3 consistently deleted in neuroblastoma. Oncogene 24:2684–2694PubMedCrossRef White PS, Thompson PM, Gotoh T, Okawa ER, Igarashi J, Kok M, Winter C, Gregory SG, Hogarty MD, Maris JM, Brodeur GM (2005) Definition and characterization of a region of 1p36.3 consistently deleted in neuroblastoma. Oncogene 24:2684–2694PubMedCrossRef
21.
Zurück zum Zitat Fujita T, Igarashi J, Okawa ER, Gotoh T, Manne J, Kolla V, Kim J, Zhao H, Pawel BR, London WB, Maris JM, White PS, Brodeur GM (2008) CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Inst 100:940–949PubMedCrossRef Fujita T, Igarashi J, Okawa ER, Gotoh T, Manne J, Kolla V, Kim J, Zhao H, Pawel BR, London WB, Maris JM, White PS, Brodeur GM (2008) CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Inst 100:940–949PubMedCrossRef
22.
23.
Zurück zum Zitat Wang J, Chen H, Fu S, Xu ZM, Sun KL, Fu WN (2011) The involvement of CHD5 hypermethylation in laryngeal squamous cell carcinoma. Oral Oncol 47:601–608PubMedCrossRef Wang J, Chen H, Fu S, Xu ZM, Sun KL, Fu WN (2011) The involvement of CHD5 hypermethylation in laryngeal squamous cell carcinoma. Oral Oncol 47:601–608PubMedCrossRef
24.
Zurück zum Zitat Wang X, Lau KK, So LK, Lam YW (2009) CHD5 is down-regulated through promoter hypermethylation in gastric cancer. J Biomed Sci 16:95PubMedCrossRef Wang X, Lau KK, So LK, Lam YW (2009) CHD5 is down-regulated through promoter hypermethylation in gastric cancer. J Biomed Sci 16:95PubMedCrossRef
25.
Zurück zum Zitat Zhao R, Yan Q, Lv J, Huang H, Zheng W, Zhang B, Ma W (2012) CHD5, a tumor suppressor that is epigenetically silenced in lung cancer. Lung Cancer 76(3):324–331 Zhao R, Yan Q, Lv J, Huang H, Zheng W, Zhang B, Ma W (2012) CHD5, a tumor suppressor that is epigenetically silenced in lung cancer. Lung Cancer 76(3):324–331
26.
Zurück zum Zitat Wong RR, Chan LK, Tsang TP, Lee CW, Cheung TH, Yim SF, Siu NS, Lee SN, Yu MY, Chim SS, Wong YF, Chung TK (2011) CHD5 downregulation associated with poor prognosis in epithelial ovarian cancer. Gynecol Obstet Invest 72:203–207PubMedCrossRef Wong RR, Chan LK, Tsang TP, Lee CW, Cheung TH, Yim SF, Siu NS, Lee SN, Yu MY, Chim SS, Wong YF, Chung TK (2011) CHD5 downregulation associated with poor prognosis in epithelial ovarian cancer. Gynecol Obstet Invest 72:203–207PubMedCrossRef
Metadaten
Titel
Decreased expression of chromodomain helicase DNA-binding protein 5 is an unfavorable prognostic marker in patients with primary gallbladder carcinoma
verfasst von
Xilin Du
Tao Wu
Jianguo Lu
Li Zang
Nuan Song
Tao Yang
Huadong Zhao
Shengzhi Wang
Publikationsdatum
01.03.2013
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 3/2013
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-012-0903-2

Weitere Artikel der Ausgabe 3/2013

Clinical and Translational Oncology 3/2013 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.