Skip to main content
Erschienen in: Journal of Neuro-Oncology 2/2014

01.06.2014 | Clinical Study

Decreased expression of LASS2 is associated with worse prognosis in meningiomas

verfasst von: Rong-Hu Ke, Yin Wang, Yin Mao, Jun Zhang, Ji Xiong

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Lamszus K (2004) Meningioma pathology, genetics, and biology. J Neuropathol Exp Neurol 63:275–286PubMed Lamszus K (2004) Meningioma pathology, genetics, and biology. J Neuropathol Exp Neurol 63:275–286PubMed
2.
Zurück zum Zitat Riemenschneider MJ, Perry A, Reifenberger G (2006) Histological classification and molecular genetics of meningiomas. Lancet Neurol 5:1045–1054PubMedCrossRef Riemenschneider MJ, Perry A, Reifenberger G (2006) Histological classification and molecular genetics of meningiomas. Lancet Neurol 5:1045–1054PubMedCrossRef
3.
Zurück zum Zitat Adegbite AB, Khan MI, Paine KW, Tan LK (1983) The recurrence of intracranial meningiomas after surgical treatment. J Neurosurg 58:51–56PubMedCrossRef Adegbite AB, Khan MI, Paine KW, Tan LK (1983) The recurrence of intracranial meningiomas after surgical treatment. J Neurosurg 58:51–56PubMedCrossRef
4.
Zurück zum Zitat Espinosa A, Tabernero MD, Maillo A et al (2006) The cytogenetic relationship between primary and recurrent meningiomas points to the need for new treatment strategies in cases at high risk of relapse. Clin Cancer Res 12:772–780PubMedCrossRef Espinosa A, Tabernero MD, Maillo A et al (2006) The cytogenetic relationship between primary and recurrent meningiomas points to the need for new treatment strategies in cases at high risk of relapse. Clin Cancer Res 12:772–780PubMedCrossRef
5.
Zurück zum Zitat Pan H, Qin WX, Huo KK et al (2001) Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1. Genomics 77:58–64PubMedCrossRef Pan H, Qin WX, Huo KK et al (2001) Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1. Genomics 77:58–64PubMedCrossRef
6.
Zurück zum Zitat Laviad EL, Albee L, Pankova-Kholmyansky I et al (2008) Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. J Biol Chem 283:5677–5684PubMedCrossRef Laviad EL, Albee L, Pankova-Kholmyansky I et al (2008) Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. J Biol Chem 283:5677–5684PubMedCrossRef
7.
Zurück zum Zitat Imgrund S, Hartmann D, Farwanah H et al (2009) Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas. J Biol Chem 284:33549–33560PubMedCentralPubMedCrossRef Imgrund S, Hartmann D, Farwanah H et al (2009) Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas. J Biol Chem 284:33549–33560PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Xu X, You J, Pei F (2012) Silencing of a novel tumor metastasis suppressor gene LASS2/TMSG1 promotes invasion of prostate cancer cell in vitro through increase of vacuolar ATPase activity. J Cell Biochem 113:2356–2363PubMedCrossRef Xu X, You J, Pei F (2012) Silencing of a novel tumor metastasis suppressor gene LASS2/TMSG1 promotes invasion of prostate cancer cell in vitro through increase of vacuolar ATPase activity. J Cell Biochem 113:2356–2363PubMedCrossRef
9.
Zurück zum Zitat Schiffmann S, Sandner J, Birod K et al (2009) Ceramide synthases and ceramide levels are increased in breast cancer tissue. Carcinogenesis 30:745–752PubMedCrossRef Schiffmann S, Sandner J, Birod K et al (2009) Ceramide synthases and ceramide levels are increased in breast cancer tissue. Carcinogenesis 30:745–752PubMedCrossRef
10.
Zurück zum Zitat Mesicek J, Lee H, Feldman T et al (2010) Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells. Cell Signal 22:1300–1307PubMedCrossRef Mesicek J, Lee H, Feldman T et al (2010) Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells. Cell Signal 22:1300–1307PubMedCrossRef
11.
Zurück zum Zitat Wang H, Wang J, Zuo Y et al (2011) Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma. Med Oncol 29:1921–1927PubMedCrossRef Wang H, Wang J, Zuo Y et al (2011) Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma. Med Oncol 29:1921–1927PubMedCrossRef
12.
Zurück zum Zitat Perry A, Louis DN, Scheithauer BW, Budka H, von Deimling A (2007) Meningiomas. In: Louis DN, Oghaki H, Wiesttler D, Cavenee WK (eds) WHO classification of tumors of the central nervous system, 4th edn. IARC Press, Lyon, pp 164–172 Perry A, Louis DN, Scheithauer BW, Budka H, von Deimling A (2007) Meningiomas. In: Louis DN, Oghaki H, Wiesttler D, Cavenee WK (eds) WHO classification of tumors of the central nervous system, 4th edn. IARC Press, Lyon, pp 164–172
13.
Zurück zum Zitat Ke HL, Ke RH, Li ST et al (2013) Expression of RACGAP1 in high grade meningiomas: a potential role in cancer progression. J Neurooncol 113:327–332PubMedCrossRef Ke HL, Ke RH, Li ST et al (2013) Expression of RACGAP1 in high grade meningiomas: a potential role in cancer progression. J Neurooncol 113:327–332PubMedCrossRef
14.
Zurück zum Zitat Barresi V, Cerasoli S, Paioli G et al (2006) Caveolin-1 in meningiomas: expression and clinicopathological correlations. Acta Neuropathol 112:617–626PubMedCrossRef Barresi V, Cerasoli S, Paioli G et al (2006) Caveolin-1 in meningiomas: expression and clinicopathological correlations. Acta Neuropathol 112:617–626PubMedCrossRef
15.
Zurück zum Zitat Fan S, Niu Y, Tan N et al (2013) LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump. Oncogene 32:1682–1690PubMedCrossRef Fan S, Niu Y, Tan N et al (2013) LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump. Oncogene 32:1682–1690PubMedCrossRef
16.
Zurück zum Zitat Nishi T, Forgac M (2002) The vacuolar H+-ATPases—nature’s most versatile proton pumps. Nat Rev Mol Cell Biol 3:94–103PubMedCrossRef Nishi T, Forgac M (2002) The vacuolar H+-ATPases—nature’s most versatile proton pumps. Nat Rev Mol Cell Biol 3:94–103PubMedCrossRef
17.
Zurück zum Zitat Otero-Rey EM, Somoza-Martín M, Barros-Angueira F, García-García A (2008) Intracellular pH regulation in oral squamous cell carcinoma is mediated by increased V-ATPase activity via over-expression of the ATP6V1C1 gene. Oral Oncol 44:193–199PubMedCrossRef Otero-Rey EM, Somoza-Martín M, Barros-Angueira F, García-García A (2008) Intracellular pH regulation in oral squamous cell carcinoma is mediated by increased V-ATPase activity via over-expression of the ATP6V1C1 gene. Oral Oncol 44:193–199PubMedCrossRef
18.
Zurück zum Zitat Petzoldt AG, Gleixner EM, Fumagalli A, Vaccari T, Simons M (2013) Elevated expression of the V-ATPase C subunit triggers JNK-dependent cell invasion and overgrowth in a Drosophila epithelium. Dis Model Mech 6:689–700PubMedCentralPubMedCrossRef Petzoldt AG, Gleixner EM, Fumagalli A, Vaccari T, Simons M (2013) Elevated expression of the V-ATPase C subunit triggers JNK-dependent cell invasion and overgrowth in a Drosophila epithelium. Dis Model Mech 6:689–700PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Lu X, Qin W, Li J et al (2005) The growth and metastasis of human hepatocellular carcinoma xenografts are inhibited by small interfering RNA targeting to the subunit ATP6L of proton pump. Cancer Res 65:6843–6849PubMedCrossRef Lu X, Qin W, Li J et al (2005) The growth and metastasis of human hepatocellular carcinoma xenografts are inhibited by small interfering RNA targeting to the subunit ATP6L of proton pump. Cancer Res 65:6843–6849PubMedCrossRef
20.
Zurück zum Zitat Yu W, Wang L, Wang Y et al (2013) A novel tumor metastasis suppressor gene LASS2/TMSG1 interacts with vacuolar ATPase through its homeodomain. J Cell Biochem 114:570–583PubMedCrossRef Yu W, Wang L, Wang Y et al (2013) A novel tumor metastasis suppressor gene LASS2/TMSG1 interacts with vacuolar ATPase through its homeodomain. J Cell Biochem 114:570–583PubMedCrossRef
Metadaten
Titel
Decreased expression of LASS2 is associated with worse prognosis in meningiomas
verfasst von
Rong-Hu Ke
Yin Wang
Yin Mao
Jun Zhang
Ji Xiong
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 2/2014
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-014-1441-2

Weitere Artikel der Ausgabe 2/2014

Journal of Neuro-Oncology 2/2014 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Schwindelursache: Massagepistole lässt Otholiten tanzen

14.05.2024 Benigner Lagerungsschwindel Nachrichten

Wenn jüngere Menschen über ständig rezidivierenden Lagerungsschwindel klagen, könnte eine Massagepistole der Auslöser sein. In JAMA Otolaryngology warnt ein Team vor der Anwendung hochpotenter Geräte im Bereich des Nackens.

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.