title: DNA microarray analysis identifies CKS2 and LEPR as potential markers of meningioma recurrence.
abstract: Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted.
authors.affiliation: Unit of Molecular Neuro-Oncology, Fondazione Istituto Neurologico Besta, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Menghi
authors.forename: Francesca N
authors.initials: FN
authors.lastname: Orzan
authors.forename: Marica
authors.initials: M
authors.lastname: Eoli
authors.forename: Mariangela
authors.initials: M
authors.lastname: Farinotti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maderna
authors.forename: Federica
authors.initials: F
authors.lastname: Pisati
authors.forename: Donatella
authors.initials: D
authors.lastname: Bianchessi
authors.forename: Lorella
authors.initials: L
authors.lastname: Valletta
authors.forename: Sandro
authors.initials: S
authors.lastname: Lodrini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Galli
authors.forename: Elena
authors.initials: E
authors.lastname: Anghileri
authors.forename: Serena
authors.initials: S
authors.lastname: Pellegatta
authors.forename: Bianca
authors.initials: B
authors.lastname: Pollo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046228:Microarray Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C515448:LEPR protein, human; D054411:Receptors, Leptin; D011494:Protein Kinases; D042846:CDC2-CDC28 Kinases; C083689:CKS2 protein, human