Cheng Xiaojing, Zheng Zhixue, Bu Zhaode, Wu Xiaojiang, Zhang Lianhai, Xing Xiaofang, Wang Xiaohong, Hu Ying, Du Hong, Li Lin, Li Shen, Zhou Rouli, Wen Xian-Zi, Ji Jia-Fu
Gastrointestinal Carcinoma Translational Research Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
PLoS One. 2015 Apr 7;10(4):e0121559. doi: 10.1371/journal.pone.0121559. eCollection 2015.
Lysosome-associated transmembrane protein 4β-35 (LAPTM4B-35), a member of the mammalian 4-tetratransmembrane spanning protein superfamily, has been reported to be overexpressed in several cancers. However the expression of LAPTM4B-35 and its role in the progression of gastric cancer (GC) remains unknown. The aim of this study was to investigate LAPTM4B-35 expression in GC, its potential relevance to clinicopathologic parameters and role of LAPTM4B-35 during gastric carcinogenesis.
In the present study, paraffin-embedded specimens with GC (n = 240, including 180 paired specimens) and 24 paired fresh frozen tissues were analyzed. qRT-PCR and immunohistochemistry (IHC) were used to analyze the expression of LAPTM4B-35 in GC. The effects of LAPTM4B-35 on GC cell proliferation, migration and invasion were determined by overexpression and knockdown assays.
IHC showed that LAPTM4B-35 was expressed in 68.3% (123/180) of GC tissues, while in 16.1% (29/180) of their paired adjacent noncancerous gastric tissues (P = 0.000). LAPTM4B-35 mRNA levels in GC tissues were also significantly elevated when compared with their paired adjacent noncancerous tissues (P = 0.017). Overexpression of LAPTM4B-35 was significantly associated with degree of differentiation, depth of invasion, lymphovascular invasion and lymph node metastasis (P<0.05). Kaplan-Meier survival curves revealed that patients with LAPTM4B-35 expression had a significant decrease in overall survival (OS) in stages I-III GC patients (P = 0.006). Multivariate analysis showed high expression of LAPTM4B-35 was an independent prognostic factor for OS in stage I-III GC patients (P = 0.025).
These findings indicate that LAPTM4B-35 overexpression may be related to GC progression and poor prognosis, and thus may serve as a new prediction marker of prognosis in GC patients.
溶酶体相关跨膜蛋白4β-35（LAPTM4B-35）是哺乳动物四跨膜蛋白超家族的成员，据报道在多种癌症中过表达。然而，LAPTM4B-35在胃癌（GC）中的表达及其在胃癌进展中的作用尚不清楚。本研究旨在探讨LAPTM4B-35在GC中的表达、其与临床病理参数的潜在相关性以及LAPTM4B-35在胃癌发生过程中的作用。
在本研究中，分析了240例GC石蜡包埋标本（包括180对配对标本）和24对新鲜冷冻组织。采用qRT-PCR和免疫组织化学（IHC）分析LAPTM4B-35在GC中的表达。通过过表达和敲低实验确定LAPTM4B-35对GC细胞增殖、迁移和侵袭的影响。
免疫组化显示，LAPTM4B-35在68.3%（123/180）的GC组织中表达，而在其配对的16.1%（29/180）相邻非癌性胃组织中表达（P = 0.000）。与配对的相邻非癌组织相比，GC组织中LAPTM4B-35 mRNA水平也显著升高（P = 0.017）。LAPTM4B-35的过表达与分化程度、浸润深度、淋巴管浸润和淋巴结转移显著相关（P<0.05）。Kaplan-Meier生存曲线显示，LAPTM4B-35表达的患者在I-III期GC患者中的总生存期（OS）显著降低（P = 0.006）。多因素分析显示，LAPTM
