title: LAPTM4B-35 is a novel prognostic factor for glioblastoma.
abstract: Lysosome-associated protein transmembrane-4 beta (LAPTM4B)-35, a newly identified cancer-associated gene, is overexpressed in a wide variety of malignant tumors. However, studies of its expression and role in glioma have not yet been reported. This study aimed to investigate the expression and the role of LAPTM4B-35 in glioma and to assess its value as a prognostic factor. Seventy-seven glioma cases (Grade II in 18 patients, Grade III in 16 and Grade IV in 43) were immunohistochemically examined for LAPTM4B-35, pAkt, factor VIII and Ki-67 expressions. The LAPTM4B-35 expression score of Grade II gliomas was lower than those of Grade III-IV gliomas (p < 0.05), while the difference between Grade III and IV gliomas was not statistically significant. Of the 43 patients with glioblastoma (GBM), 27 (62.8%) had high LAPTM4B-35 expression, which was associated with high tumor micro-vessel density and pAkt activation. The median progression-free survival (PFS) of GBM patients with high LAPTM4B-35 expression was 5.13 months, significantly shorter than that of those with low LAPTM4B-35 expression (12.0 months, p < 0.0001). The median overall survival (OS) of GBM patients with high LAPTM4B-35 expression was 12.5 months, again significantly shorter than that of those with low LAPTM4B-35 expression (29.6 months, p < 0.0001). Multivariate analysis indicated LAPTM4B-35 to be an independent prognostic factor for PFS and OS of GBM patients. Our findings show LAPTM4B-35 to be strongly associated with tumor proliferation, tumor angiogenesis and poor outcomes of GBM patients, suggesting LAPTM4B-35 to potentially be applicable as a novel prognostic marker and even to possibly play a role in improving GBM treatment.
authors.affiliation: Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Xiaoshud
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. kaoru-tmd@umin.ac.jp.
authors.forename: Kaoru
authors.identifier: http://orcid.org/0000-0002-7943-5458
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Department of Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Ando
authors.affiliation: Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Sumita
authors.affiliation: Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Maehara
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000150:complications / Q000378:metabolism* / Q000401:mortality; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000150:complications / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008745:Methylation; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000209:etiology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; C100848:LAPTM5 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D051058:Oncogene Protein v-akt; D045643:DNA Repair Enzymes
keywords: Angiogenesis; Glioblastoma; LAPTM4B-35; P-Akt; Prognosis