Dong Xiaoshud, Tamura Kaoru, Kobayashi Daisuke, Ando Noboru, Sumita Kazutaka, Maehara Taketoshi
Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Department of Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
J Neurooncol. 2017 Apr;132(2):295-303. doi: 10.1007/s11060-017-2369-0. Epub 2017 Jan 18.
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.
溶酶体相关蛋白跨膜4β（LAPTM4B）-35是一个新发现的癌症相关基因，在多种恶性肿瘤中过表达。然而，其在胶质瘤中的表达及作用尚未见报道。本研究旨在探讨LAPTM4B-35在胶质瘤中的表达及作用，并评估其作为预后因素的价值。对77例胶质瘤病例（18例二级、16例三级和43例四级）进行免疫组织化学检测，分析LAPTM4B-35、pAkt、因子VIII和Ki-67的表达情况。二级胶质瘤的LAPTM4B-35表达评分低于三级和四级胶质瘤（p＜0.05），而三级和四级胶质瘤之间的差异无统计学意义。在43例胶质母细胞瘤（GBM）患者中，27例（62.8%）LAPTM4B-35表达较高，这与高肿瘤微血管密度和pAkt激活相关。LAPTM4B-35高表达的GBM患者的无进展生存期（PFS）中位数为5.13个月，显著短于LAPTM4B-35低表达患者（12.0个月，p＜0.0001）。LAPTM4B-35高表达的GBM患者的总生存期（OS）中位数为12.5个月，同样显著短于LAPTM4B-35低表达患者（29.6个月，p＜0.0001）。多因素分析表明，LAPTM4B-35是GBM患者PFS和OS的独立预后因素。我们的研究结果表明，LAPTM4B-35与肿瘤增殖、肿瘤血管生成及GBM患者的不良预后密切相关，提示LAPTM4B-35可能作为一种新的预后标志物，甚至可能在改善GBM治疗中发挥作用。
