期刊论文详细信息
Journal of Translational Medicine
Flotillin-2 is associated with breast cancer progression and poor survival outcomes
Huan-Xin Lin4  Li-Bing Song3  Xiao-Hui Zhao3  Xing-Hua Li3  Ling Guo1  Qi Yang1  Xi Wang2 
[1] Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China;Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China;Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China;State Key Laboratory of Oncology in South China and Department of Radiation Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Dong Road, Guangzhou 510060, PR China
关键词: Biomarker;    Prognosis;    Breast cancer;    FLOT2;   
Others  :  826907
DOI  :  10.1186/1479-5876-11-190
 received in 2013-05-28, accepted in 2013-08-13,  发布年份 2013
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【 摘 要 】

Background

Flotillin-2 (FLOT2) has been implicated in several signaling pathways in tumor cells. Our study aimed to investigate the expression pattern and clinicopathological significance of FLOT2 in patients with breast cancer.

Methods

The expression level of FLOT2 in normal breast epithelial cells, breast cancer cell lines, and four breast cancer biopsies paired with adjacent noncancerous tissues were quantified using real-time RT-PCR and Western blotting. FLOT2 protein expression was analyzed in 171 archived paraffin-embedded breast cancer samples using immunohistochemistry (IHC). Statistical analyses were performed to evaluate the clinicopathological significance of FLOT2 expression.

Results

FLOT2 was significantly upregulated in breast cancer cell lines and tissue samples compared with normal cells and adjacent noncancerous breast tissues, respectively. IHC analysis revealed high expression levels of FLOT2 in 82 of 171 (48.0%) breast cancer specimens. Statistical analysis revealed that FLOT2 expression was significantly correlated with clinical stage (P < 0.001), T classification (P < 0.001), M classification (P < 0.001), histological differentiation (P = 0.005) and ErbB2 expression (P = 0.003). Patients with higher levels of FLOT2 expression had a shorter overall survival duration than patients with lower FLOT2 expression levels. Multivariate analysis suggested that FLOT2 expression was an independent prognostic marker for survival in patients with breast cancer.

Conclusions

The current results demonstrated that high FLOT2 protein expression was associated with poor outcomes in patients with breast cancer. FLOT2 could be used as a prognostic biomarker for breast cancer progression.

【 授权许可】

   
2013 Wang et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
  • [2]Robbins P, Pinder S, De Klerk N, Dawkins H, Harvey J, Sterrett G, Ellis I, Elston C: Histological grading of breast carcinomas: a study of interobserver agreement. Hum Pathol 1995, 26:873-879.
  • [3]Elston CW, Ellis IO: Pathological prognostic factors in breast cancer I: the value of histological gradeinbreast cancer: experience from a large study with long-term follow-up. Histopathology 1991, 19:403-410.
  • [4]Galea MH, Blamey RW, Elston CE, Ellis IO: The Nottingham prognostic index in primary breast cancer. Breast Cancer Res Treat 1992, 22:207-219.
  • [5]Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, Ruby SG, O’Malley F, Simpson JF, Connolly JL, Hayes DF, Edge SB, Lichter A, Schnitt SJ: Prognostic factors in breast cancer: College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000, 124:966-978.
  • [6]Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature 2000, 406:747-752.
  • [7]Schulte T, Paschke KA, Laessing U, Lottspeich F, Stuermer CA: Reggie-1 and reggie-2, two cell surface proteins expressed by retinal ganglion cells during axon regeneration. Development 1997, 124:577-587.
  • [8]Lang DM, Lommel S, Jung M, Ankerhold R, Petrausch B, Laessing U, Wiechers MF, Plattner H, Stuermer CA: Identification of reggie-1 and reggie-2 as plasmamembrane-associated proteins which cocluster with activated GPI-anchored cell adhesion molecules in non-caveolar micropatches in neurons. J Neurobiol 1998, 37:502-523.
  • [9]Munro S: Lipid rafts: elusive or illusive? Cell 2003, 115:377-388.
  • [10]Carver LA, Schnitzer JE, Anderson RG, Mohla S: Role of caveolae and lipid rafts in cancer: workshop summary and future needs. Cancer Res 2003, 63:6571-6574.
  • [11]Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 2000, 1:31-39.
  • [12]Hazarika P, McCarty MF, Prieto VG, George S, Babu D, Koul D, Bar-Eli M, Duvic M: Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Cancer Res 2004, 64:7361-7369.
  • [13]Rickman DS, Millon R, De Reynies A, Thomas E, Wasylyk C, Muller D, Abecassis J, Wasylyk B: Prediction of future metastasis and molecular characterization of head and neck squamous-cell carcinoma based on transcriptome and genome analysis by microarrays. Oncogene 2008, 27:6607-6622.
  • [14]Pust S, Klokk TI, Musa N, Jenstad M, Risberg B, Erikstein B, Tcatchoff L, Liestøl K, Danielsen HE, Van Deurs B, Sandvig K: Flotillins as regulators of ErbB2 levels in breast cancer. Oncogene 2013, 32:3443-3451.
  • [15]Berger T, Ueda T, Arpaia E, Chio II, Shirdel EA, Jurisica I, Hamada K, You-Ten A, Haight J, Wakeham A, Cheung CC, Mak TW: Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model. Oncogenein press
  • [16]Li J, Zhang N, Song LB, Liao WT, Jiang LL, Gong LY, Wu J, Yuan J, Zhang HZ, Zeng MS, Li M: Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival. Clin Cancer Res 2008, 14:3319-3326.
  • [17]Satyamoorthy K, Li G, Gerrero MR, Brose MS, Volpe P, Weber BL, Van Belle P, Elder DE, Herlyn M: Constitutive mitogen activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res 2003, 63:756-759.
  • [18]McAuliffe PF, Meric-Bernstam F, Mills GB, Gonzalez-Angulo AM: Deciphering the role of PI3K/Akt/mTOR pathway in breast cancer biology and pathogenesis. Clin Breast Cancer 2010, 10(Suppl 3):59-65.
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