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Diagnostic Pathology

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Open Access 01-12-2015 | Research

Prognostic significance of FAM3C in esophageal squamous cell carcinoma

Authors: Ying-Hui Zhu, Baozhu Zhang, Mengqing Li, Pinzhu Huang, Jian Sun, Jianhua Fu, Xin-Yuan Guan

Published in: Diagnostic Pathology | Issue 1/2015

Abstract

Background

Family with sequence similarity 3, member C (FAM3C) has been identified as a novel regulator in epithelial-mesenchymal transition (EMT) and metastatic progression. However, the role of FAM3C in esophageal squamous cell carcinoma (ESCC) remains unexplored. The purpose of present study is to illustrate the role of FAM3C in predicting outcomes of patients with ESCC.

Methods

FAM3C expression was measured in ESCC tissues and the matched adjacent nontumorous tissues by quantitative real-time RT-PCR and Western blot analysis. The relationship between FAM3C expression and prognosis of ESCC patients was further evaluated by univariate and multivariate regression analyses. Univariate and multivariate analyses of the prognostic factors were performed using Cox proportional hazards model.

Results

The FAM3C mRNA expression was remarkably upregulated in ESCC compared with their nontumor counterparts (P < 0.001). In addition, high expression of FAM3C was significantly associated with pT stage (P = 0.014) , pN stage (P = 0.026) and TNM stage (P = 0.003). Kaplan-Meier analysis showed that the 7-year overall survival rate in the group with high expression of FAM3C was poorer than that in low expression group (32.0 versus 70.9 %; P < 0.001). Univariate and multivariate analyses demonstrated that FAM3C was an independent risk factor for overall survival. Moreover, Stratified analysis revealed that FAM3C expression could differentiate the prognosis of patients in early clinical stage (TNM stage I-II).

Conclusions

FAM3C expression was dramatically increased in ESCC and might serve as a valuable prognostic indicator for ESCC patients after surgery.

Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50. doi:10.1200/JCO.2005.05.2308.CrossRefPubMed

Wheeler JB, Reed CE. Epidemiology of esophageal cancer. Surg Clin North Am. 2012;92(5):1077–87. doi:10.1016/j.suc.2012.07.008.CrossRefPubMed

Hongo M, Nagasaki Y, Shoji T. Epidemiology of esophageal cancer: orient to occident. Effects of chronology, geography and ethnicity. J Gastroenterol Hepatol. 2009;24(5):729–35. doi:10.1111/j.1440-1746.2009.05824.x.CrossRefPubMed

Stoner GD, Gupta A. Etiology and chemoprevention of esophageal squamous cell carcinoma. Carcinogenesis. 2001;22(11):1737–46.CrossRefPubMed

Xiao ZF, Yang ZY, Liang J, Miao YJ, Wang M, Yin WB, et al. Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients. Ann Thorac Surg. 2003;75(2):331–6.CrossRefPubMed

Shimizu K, Hihara J, Yoshida K, Toge T. Clinical evaluation of low-dose cisplatin and 5-fluorouracil as adjuvant chemoradiotherapy for advanced squamous cell carcinoma of the esophagus. Hiroshima J Med Sci. 2005;54(3):67–71.PubMed

Hagymasi K, Tulassay Z. Risk factors for esophageal cancer, and possible genetic background. Orv Hetil. 2009;150(9):407–13. doi:10.1556/OH.2009.28558.CrossRefPubMed

Zhu Y, Xu G, Patel A, McLaughlin MM, Silverman C, Knecht K, et al. Cloning, expression, and initial characterization of a novel cytokine-like gene family. Genomics. 2002;80(2):144–50.CrossRefPubMed

Greinwald Jr JH, Wayne S, Chen AH, Scott DA, Zbar RI, Kraft ML, et al. Localization of a novel gene for nonsyndromic hearing loss (DFNB17) to chromosome region 7q31. Am J Med Genet. 1998;78(2):107–13.CrossRefPubMed

10.

Waerner T, Alacakaptan M, Tamir I, Oberauer R, Gal A, Brabletz T, et al. ILEI: a cytokine essential for EMT, tumor formation, and late events in metastasis in epithelial cells. Cancer Cell. 2006;10(3):227–39. doi:10.1016/j.ccr.2006.07.020.CrossRefPubMed

11.

Chaudhury A, Hussey GS, Ray PS, Jin G, Fox PL, Howe PH. TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI. Nat Cell Biol. 2010;12(3):286–93. doi:10.1038/ncb2029.PubMedCentralPubMed

12.

Gronborg M, Kristiansen TZ, Iwahori A, Chang R, Reddy R, Sato N, et al. Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol Cell Proteomics. 2006;5(1):157–71. doi:10.1074/mcp.M500178-MCP200.CrossRefPubMed

13.

Gao ZH, Lu C, Wang ZN, Song YX, Zhu JL, Gao P, et al. ILEI: a novel marker for epithelial-mesenchymal transition and poor prognosis in colorectal cancer. Histopathology. 2014;65(4):527–38. doi:10.1111/his.12435.CrossRefPubMed

14.

Rice TW, Rusch VW, Ishwaran H, Blackstone EH, Worldwide Esophageal Cancer C. Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals. Cancer. 2010;116(16):3763–73. doi:10.1002/cncr.25146.CrossRefPubMed

15.

Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90. doi:10.1016/j.cell.2009.11.007.CrossRefPubMed

16.

Grunert S, Jechlinger M, Beug H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol. 2003;4(8):657–65. doi:10.1038/nrm1175.CrossRefPubMed

17.

Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, et al. Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. J Cell Physiol. 2007;213(2):374–83. doi:10.1002/jcp.21223.CrossRefPubMed

18.

Katsuno Y, Lamouille S, Derynck R. TGF-beta signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 2013;25(1):76–84. doi:10.1097/CCO.0b013e32835b6371.CrossRefPubMed

19.

Willis BC, Borok Z. TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol. 2007;293(3):L525–34. doi:10.1152/ajplung.00163.2007.CrossRefPubMed

20.

Hussey GS, Chaudhury A, Dawson AE, Lindner DJ, Knudsen CR, Wilce MC, et al. Identification of an mRNP complex regulating tumorigenesis at the translational elongation step. Mol Cell. 2011;41(4):419–31. doi:10.1016/j.molcel.2011.02.003.PubMedCentralCrossRefPubMed

21.

Hussey GS, Link LA, Brown AS, Howley BV, Chaudhury A, Howe PH. Establishment of a TGFbeta-induced post-transcriptional EMT gene signature. PLoS One. 2012;7(12):e52624. doi:10.1371/journal.pone.0052624.PubMedCentralCrossRefPubMed

22.

Song Q, Sheng W, Zhang X, Jiao S, Li F. ILEI drives epithelial to mesenchymal transition and metastatic progression in the lung cancer cell line A549. Tumour Biol. 2014;35(2):1377–82. doi:10.1007/s13277-013-1188-y.CrossRefPubMed

23.

Du Plessis L, Dietzsch E, Van Gele M, Van Roy N, Van Helden P, Parker MI, et al. Mapping of novel regions of DNA gain and loss by comparative genomic hybridization in esophageal carcinoma in the Black and Colored populations of South Africa. Cancer Res. 1999;59(8):1877–83.PubMed

24.

Kwong D, Lam A, Guan X, Law S, Tai A, Wong J, et al. Chromosomal aberrations in esophageal squamous cell carcinoma among Chinese: gain of 12p predicts poor prognosis after surgery. Hum Pathol. 2004;35(3):309–16.CrossRefPubMed

25.

Lahsnig C, Mikula M, Petz M, Zulehner G, Schneller D, van Zijl F, et al. ILEI requires oncogenic Ras for the epithelial to mesenchymal transition of hepatocytes and liver carcinoma progression. Oncogene. 2009;28(5):638–50. doi:10.1038/onc.2008.418.PubMedCentralCrossRefPubMed

26.

Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2(8):563–72. doi:10.1038/nrc865.CrossRefPubMed

27.

Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117(7):927–39. doi:10.1016/j.cell.2004.06.006.CrossRefPubMed

28.

Leptin M, Grunewald B. Cell shape changes during gastrulation in Drosophila. Development. 1990;110(1):73–84.PubMed

29.

Nguyen DX, Massague J. Genetic determinants of cancer metastasis. Nat Rev Genet. 2007;8(5):341–52. doi:10.1038/nrg2101.CrossRefPubMed

30.

Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147(2):275–92. doi:10.1016/j.cell.2011.09.024.PubMedCentralCrossRefPubMed

Title: Prognostic significance of FAM3C in esophageal squamous cell carcinoma
Authors: Ying-Hui Zhu
Baozhu Zhang
Mengqing Li
Pinzhu Huang
Jian Sun
Jianhua Fu
Xin-Yuan Guan
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-015-0424-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Prognostic significance of FAM3C in esophageal squamous cell carcinoma

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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