title: Prognostic significance of sphingosine kinase 2 expression in non-small cell lung cancer.
abstract: Sphingosine kinase 2 (SphK2) as a conserved lipid kinase has not been thoroughly elucidated in non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the expression of SphK2 in NSCLC tissues and to determine its correlation with clinicopathologic characteristics and its impact on patient prognosis. We assessed the expression of SphK2 and proliferating cell nuclear antigen (PCNA) (as a proliferative index) by immunohistochemistry in 180 NSCLC patient's formalin-fixed paraffin-embedded tissue blocks. Relationship between the expression of SphK2 and PCNA and various clinicopathological features in these patients was evaluated. We detected that expression of SphK2 was gradually upregulated from normal, metaplasia/dysplasia tissues to NSCLC tissues. At the same time, PCNA expression followed a similar pattern. Statistical analysis showed that expression of SphK2 in NSCLC tissues was strongly associated with PCNA expression, histology grade, live vaccine strain invasion, lymph node status, clinical stage, tumors size, and histology type. Patients with SphK2 overexpression in their tissues had lower overall survival (OS) and disease-free survival (DFS) rates than those with low SphK2 expression. Using uni- and multivariate analysis, we found that SphK2 overexpression was an independent prognostic factor for both OS and DFS. The expression of SphK2 parallels the progression of NSCLC, and SphK2 overexpression may represent a novel and potentially independent biomarker for the prognosis of patients with NSCLC.
authors.affiliation: Department of Cardiothoracic Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Wang
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.forename: Guanghua
authors.initials: G
authors.lastname: Li
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Li
authors.forename: Chunlin
authors.initials: C
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Guangquan
authors.initials: G
authors.lastname: Xu
authors.forename: Songbin
authors.initials: S
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D047368:Tumor Burden; D000099157:Sphingosine Kinase
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); D018809:Proliferating Cell Nuclear Antigen; D000099157:Sphingosine Kinase
references.citation: Breast Cancer Res Treat. 2008 Nov;112(1):41-52
references.pmid: 18058224
references.citation: Nature. 1996 Jun 27;381(6585):800-3
references.pmid: 8657285
references.citation: J Thorac Oncol. 2007 Aug;2(8):706-14
references.pmid: 17762336
references.citation: J Cell Biol. 1999 Nov 1;147(3):545-58
references.pmid: 10545499
references.citation: Mol Cell Biol. 2008 Jun;28(12):4142-51
references.pmid: 18426913
references.citation: J Pharmacol Exp Ther. 2010 Apr;333(1):129-39
references.pmid: 20061445
references.citation: Tumour Biol. 2013 Dec;34(6):3939-44
references.pmid: 23838802
references.citation: Int J Biol Macromol. 2012 Dec;51(5):968-73
references.pmid: 22750577
references.citation: Nat Rev Cancer. 2004 Aug;4(8):604-16
references.pmid: 15286740
references.citation: J Biol Chem. 2003 Nov 21;278(47):46832-9
references.pmid: 12954646
references.citation: Tumour Biol. 2012 Jun;33(3):629-40
references.pmid: 22446937
references.citation: Cancer Res. 2007 Nov 1;67(21):10466-74
references.pmid: 17974990
references.citation: J Biol Chem. 2005 Aug 19;280(33):29462-9
references.pmid: 15951439
references.citation: Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):150-5
references.pmid: 9419344
references.citation: Mol Cancer Res. 2011 Nov;9(11):1509-19
references.pmid: 21896638
references.citation: Tohoku J Exp Med. 2009 Jan;217(1):29-35
references.pmid: 19155605
references.citation: J Biol Chem. 2003 Oct 10;278(41):40330-6
references.pmid: 12835323
references.citation: Curr Drug Targets. 2008 Aug;9(8):662-73
references.pmid: 18691013
references.citation: Adv Cancer Res. 2013;117:201-35
references.pmid: 23290781
references.citation: FASEB J. 2009 Feb;23(2):405-14
references.pmid: 18824518
references.citation: Exp Mol Med. 2004 Oct 31;36(5):411-9
references.pmid: 15557813
references.citation: Cells Tissues Organs. 2010;192(5):314-24
references.pmid: 20606403
references.citation: J Neuropathol Exp Neurol. 2005 Aug;64(8):695-705
references.pmid: 16106218
references.citation: Clin Cancer Res. 2008 Nov 1;14(21):6996-7003
references.pmid: 18980995
references.citation: Int J Biol Macromol. 2013 Jun;57:22-5
references.pmid: 23500436
references.citation: Int J Biol Macromol. 2012 Nov;51(4):663-7
references.pmid: 22771925