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Down-regulation of tumor suppressor in lung cancer 1 (TSLC1) expression correlates with poor prognosis in patients with colon cancer

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Abstract

Tumor suppressor in lung cancer 1 (TSLC1), a novel tumor suppressor gene, has been reported to be frequently inactivated in a variety of human malignant tumors. The aim of this study was to detect TSLC1 expression in human colon cancer and to analyze its association with prognosis of patients with colon cancer. Using quantitative real-time PCR and Western blot analysis, we found significantly decreased expression of TSLC1 in primary colon tumor tissues (n = 30) compared with adjacent normal tissues. Immunohistochemistry analysis also found decreased TSLC1 expression in 41.3 % (33/80) colon tumor tissues. In clinicopathological analysis, loss of TSLC1 expression significantly correlated with female gender and lymph node metastasis of colon cancer patients (P < 0.05). In addition, decreased expression of TSLC1 in tumors was found to be closely associated with a poor prognosis (P = 0.037, log-rank test), and multivariate analysis showed that lower TSLC1 protein expression was an independent prognostic factor for colon cancer patients. Our study suggests that down-regulated expression of TSLC1 may play an important role in the progression of colon cancer and TSLC1 expression may serve as a useful marker for the prognostic evaluation of patients with colon cancer.

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References

  • Ando K, Ohira M, Ozaki T, Nakagawa A, Akazawa K, Suenaga Y, Nakamura Y, Koda T, Kamijo T, Murakami Y, Nakagawara A (2008) Expression of TSLC1, a candidate tumor suppressor gene mapped to chromosome 11q23, is downregulated in unfavorable neuroblastoma without promoter hypermethylation. Int J Cancer 123(9):2087–2094. doi:10.1002/ijc.23776

    Article  PubMed  CAS  Google Scholar 

  • Chen K, Wang G, Peng L, Liu S, Fu X, Zhou Y, Yu H, Li A, Li J, Zhang S, Bai Y, Zhang Y (2011) CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease. Int J Cancer 128(2):266–273. doi:10.1002/ijc.25356

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Zhang Y, Zhang X, Li J, Han B, Liu S, Wang L, Ling Y, Mao S, Wang X (2012) Overexpression of integrin-linked kinase correlates with malignant phenotype in non-small cell lung cancer and promotes lung cancer cell invasion and migration via regulating epithelial-mesenchymal transition (EMT)-related genes. Acta Histochem. doi:10.1016/j.acthis.2012.05.004

  • Fukami T, Fukuhara H, Kuramochi M, Maruyama T, Isogai K, Sakamoto M, Takamoto S, Murakami Y (2003) Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines. Int J Cancer 107(1):53–59. doi:10.1002/ijc.11348

    Article  PubMed  CAS  Google Scholar 

  • Goto A, Niki T, Chi-Pin L, Matsubara D, Murakami Y, Funata N, Fukayama M (2005) Loss of TSLC1 expression in lung adenocarcinoma: relationships with histological subtypes, sex and prognostic significance. Cancer Sci 96(8):480–486. doi:10.1111/j.1349-7006.2005.00075.x

    Article  PubMed  CAS  Google Scholar 

  • Heller G, Geradts J, Ziegler B, Newsham I, Filipits M, Markis-Ritzinger EM, Kandioler D, Berger W, Stiglbauer W, Depisch D, Pirker R, Zielinski CC, Zochbauer-Muller S (2007) Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer. Breast Cancer Res Treat 103(3):283–291. doi:10.1007/s10549-006-9377-7

    Article  PubMed  CAS  Google Scholar 

  • Hong Y, Downey T, Eu KW, Koh PK, Cheah PY (2010) A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics. Clin Exp Metastasis 27(2):83–90. doi:10.1007/s10585-010-9305-4

    Article  PubMed  CAS  Google Scholar 

  • Hui AB, Lo KW, Kwong J, Lam EC, Chan SY, Chow LS, Chan AS, Teo PM, Huang DP (2003) Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol Carcinog 38(4):170–178. doi:10.1002/mc.10156

    Article  PubMed  CAS  Google Scholar 

  • Ito T, Shimada Y, Hashimoto Y, Kaganoi J, Kan T, Watanabe G, Murakami Y, Imamura M (2003) Involvement of TSLC1 in progression of esophageal squamous cell carcinoma. Cancer Res 63(19):6320–6326

    PubMed  CAS  Google Scholar 

  • Jansen M, Fukushima N, Rosty C, Walter K, Altink R, Heek TV, Hruban R, Offerhaus JG, Goggins M (2002) Aberrant methylation of the 5′ CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanlNs. Cancer Biol Ther 1(3):293–296

    PubMed  CAS  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107

    Article  PubMed  Google Scholar 

  • Kuramochi M, Fukuhara H, Nobukuni T, Kanbe T, Maruyama T, Ghosh HP, Pletcher M, Isomura M, Onizuka M, Kitamura T, Sekiya T, Reeves RH, Murakami Y (2001) TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer. Nat Genet 27(4):427–430. doi:10.1038/86934

    Article  PubMed  CAS  Google Scholar 

  • Liang QL, Chen GQ, Li ZY, Wang BR (2011) Function and histopathology of a cell adhesion molecule TSLC1 in cancer. Cancer Invest 29(2):107–112

    Article  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262

    Article  PubMed  CAS  Google Scholar 

  • Lung HL, Cheung AK, Xie D, Cheng Y, Kwong FM, Murakami Y, Guan XY, Sham JS, Chua D, Protopopov AI, Zabarovsky ER, Tsao SW, Stanbridge EJ, Lung ML (2006) TSLC1 is a tumor suppressor gene associated with metastasis in nasopharyngeal carcinoma. Cancer Res 66(19):9385–9392. doi:10.1158/0008-5472.CAN-06-0590

    Article  PubMed  CAS  Google Scholar 

  • Masuda M, Yageta M, Fukuhara H, Kuramochi M, Maruyama T, Nomoto A, Murakami Y (2002) The tumor suppressor protein TSLC1 is involved in cell–cell adhesion. J Biol Chem 277(34):31014–31019. doi:10.1074/jbc.M203620200

    Article  PubMed  CAS  Google Scholar 

  • Ochiai H, Takenobu H, Nakagawa A, Yamaguchi Y, Kimura M, Ohira M, Okimoto Y, Fujimura Y, Koseki H, Kohno Y, Nakagawara A, Kamijo T (2010) Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma. Oncogene 29(18):2681–2690. doi:10.1038/onc.2010.22

    Article  PubMed  CAS  Google Scholar 

  • Punt CJ, Tol J (2009) More is less: combining targeted therapies in metastatic colorectal cancer. Nat Rev Clin Oncol 6(12):731–733. doi:10.1038/nrclinonc.2009.168

    Article  PubMed  CAS  Google Scholar 

  • Sobin LH, Fleming ID (1997) TNM Classification of malignant tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 80(9):1803–1804. doi:10.1002/(SICI)1097-0142(19971101)80:9<1803

    Google Scholar 

  • Steenbergen RD, Kramer D, Braakhuis BJ, Stern PL, Verheijen RH, Meijer CJ, Snijders PJ (2004) TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst 96(4):294–305

    Article  PubMed  CAS  Google Scholar 

  • Takahashi Y, Iwai M, Kawai T, Arakawa A, Ito T, Sakurai-Yageta M, Ito A, Goto A, Saito M, Kasumi F, Murakami Y (2012) Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer. Breast Cancer. 19(3):242–252. doi:10.1007/s12282-011-0272-7

    Google Scholar 

  • Yang YX, Yang AH, Yang ZJ, Wang ZR, Xia XH (2006) Involvement of tumor suppressor in lung cancer 1 gene expression in cervical carcinogenesis. Int J Gynecol Cancer 16(5):1868–1872. doi:10.1111/j.1525-1438.2006.00656.x

    Article  PubMed  Google Scholar 

  • Yang G, He W, Cai M, Luo F, Kung H, Guan X, Zeng Y, Xie D (2011) Loss/Down-regulation of tumor suppressor in lung cancer 1 expression is associated with tumor progression and is a biomarker of poor prognosis in ovarian carcinoma. Int J Gynecol Cancer 21(3):486–493. doi:10.1097/IGC.0b013e31820fa168

    Article  PubMed  Google Scholar 

  • Yang W, Cui S, Ma J, Lu Q, Kong C, Liu T, Sun Z (2012) Cigarette smoking extract causes hypermethylation and inactivation of WWOX gene in T-24 human bladder cancer cells. Neoplasma 59(2):216–223

    Article  PubMed  CAS  Google Scholar 

  • You Y, Ma L, You M, Li X, Wang S, Li H, Wu D, Yang H, Li ZY (2010) TSLC1 gene silencing in cutaneous melanoma. Melanoma Res 20(3):179–183. doi:10.1097/CMR.0b013e32833413c0

    PubMed  CAS  Google Scholar 

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Correspondence to Xinshu Dong.

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Zhang, J., Ning, J., Geng, J. et al. Down-regulation of tumor suppressor in lung cancer 1 (TSLC1) expression correlates with poor prognosis in patients with colon cancer. J Mol Hist 43, 715–721 (2012). https://doi.org/10.1007/s10735-012-9438-7

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  • DOI: https://doi.org/10.1007/s10735-012-9438-7

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