title: Decreased expression of LASS2 is associated with worse prognosis in meningiomas.
abstract: Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2) has been indicated to have a critical role in various tumors. In the study, we aimed to evaluate the LASS2 expression level in prognostic significance and compare it with commonly used biomarkers: Ki-67, p53 and progesterone receptor (PR) for patients with meningiomas. Firstly, 50 fresh tissues and 143 paraffin-embedded meningiomas samples were analyzed for LASS2 expression by quantitative PCR and immunohistochemistry (IHC), respectively. Subsequently, LASS2 immunostaining was evaluated for its clinical significance. Furthermore, Correlations of LASS2 expression with common biomarkers were assessed. Both PCR and IHC results showed LASS2 was downregulated in high-grade meningiomas in comparison with that of grade I or normal brain (all P < 0.01). IHC results demonstrated LASS2 intensity distribution (ID) score was significantly correlated with tumor size, brain invasion, tumor recurrence and clinical course (all P < 0.01), whereas no correlation of LASS2 ID score with sex or Simpson grade. Moreover, lower LASS2 ID score was strikingly associated with shorter overall and progression-free survival (P < 0.01). Pearson's analysis revealed the ID score was significantly reversely associated with Ki-67 and p53 but not with PR. More importantly,multivariate analyses revealed that LASS2 was an independent prognostic factor (P < 0.05). To our knowledge, it is the first time to investigate the expression of LASS2 and identify it as a potential biomarker for prognosis in meningiomas.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Huashan Hospital, Fudan University School of Medicine, Shanghai, China.
authors.forename: Rong-Hu
authors.initials: RH
authors.lastname: Ke
authors.affiliation: Department of Neuropathology, Institute of Neurology and Huashan Hospital of Fudan University School of Medicine, No. 12 the Middle Wu Lu Mu Qi Road, Shanghai, 200040, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University School of Medicine, Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neuropathology, Institute of Neurology and Huashan Hospital of Fudan University School of Medicine, No. 12 the Middle Wu Lu Mu Qi Road, Shanghai, 200040, China. 062101043@fudan.edu.cn.
authors.forename: Ji
authors.initials: J
authors.lastname: Xiong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D002648:Child; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008579:Meningioma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D051049:Sphingosine N-Acyltransferase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C438311:CERS2 protein, human; D051049:Sphingosine N-Acyltransferase
references.citation: J Biol Chem. 2008 Feb 29;283(9):5677-84
references.pmid: 18165233
references.citation: J Cell Biochem. 2012 Jul;113(7):2356-63
references.pmid: 22573553
references.citation: Lancet Neurol. 2006 Dec;5(12):1045-54
references.pmid: 17110285
references.citation: J Neurosurg. 1983 Jan;58(1):51-6
references.pmid: 6847909
references.citation: Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):772-80
references.pmid: 16467088
references.citation: Nat Rev Mol Cell Biol. 2002 Feb;3(2):94-103
references.pmid: 11836511
references.citation: Genomics. 2001 Sep;77(1-2):58-64
references.pmid: 11543633
references.citation: Med Oncol. 2012 Sep;29(3):1921-7
references.pmid: 21755371
references.citation: Cell Signal. 2010 Sep;22(9):1300-7
references.pmid: 20406683
references.citation: J Neurooncol. 2013 Jun;113(2):327-32
references.pmid: 23525949
references.citation: Oncogene. 2013 Mar 28;32(13):1682-90
references.pmid: 22580606
references.citation: Dis Model Mech. 2013 May;6(3):689-700
references.pmid: 23335205
references.citation: Oral Oncol. 2008 Feb;44(2):193-9
references.pmid: 17467328
references.citation: Carcinogenesis. 2009 May;30(5):745-52
references.pmid: 19279183
references.citation: Acta Neuropathol. 2006 Nov;112(5):617-26
references.pmid: 16850311
references.citation: J Neuropathol Exp Neurol. 2004 Apr;63(4):275-86
references.pmid: 15099018
references.citation: Cancer Res. 2005 Aug 1;65(15):6843-9
references.pmid: 16061667
references.citation: J Cell Biochem. 2013 Mar;114(3):570-83
references.pmid: 22991218
references.citation: J Biol Chem. 2009 Nov 27;284(48):33549-60
references.pmid: 19801672