Department of Clinical Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Beijing Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
BMC Cancer. 2019 Apr 2;19(1):293. doi: 10.1186/s12885-019-5506-7.
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B), a novel oncogene, promotes tumorigenesis and may be a potential prognostic biomarker in several cancers. This study was to determine the clinical significance and biological roles of LAPTM4B in lung adenocarcinoma (LAC).
LAPTM4B expression was analyzed by immunohistochemistry (IHC) of 63 LAC tumors. Serum levels of LAPTM4B were measured by enzyme-linked immuosorbent assays (ELISA). The study included untreated group (n = 216), chemotherapy group (n = 29), chemotherapy efficacy group (n = 179), EGFR-TKIs group (n = 57) and 68 healthy controls. Statistical analysis was performed to explore the correlation between LAPTM4B expression and clinicopathological parameters in LAC. Kaplan-Meier analysis was performed to assess the prognostic significance of LAPTM4B in LAC. In vitro assays were performed to assess the biological roles of LAPTM4B in LAC cells. Western blotting assays were examined to identify the underlying pathways involved in the tumor-promoting role of LAPTM4B.
We found LAPTM4B was upregulated in LAC tissues and high LAPTM4B expression was significantly correlated with poor prognosis. Serum LAPTM4B levels were significantly decreased after chemotherapy. Patients in invalid response group showed higher LAPTM4B levels than the valid response group. Overexpression of LAPTM4B promoted, while silencing of LAPTM4B inhibited proliferation, invasion and migration of LAC cells via PI3K/AKT and EMT signals. LAPTM4B expression level was associated with epidermal growth factor receptor (EGFR) gene mutations. In addition, LAPTM4B plays important roles in EGFR-promoted cell proliferation, migration and invasion and gefitinib-induced apoptosis.
Collectively, our data propose that LAPTM4B may be a cancer biomarker for LAC and a potential therapeutic target which facilitates the development of a novel therapeutic strategy against LAC.
溶酶体相关蛋白跨膜 4β（LAPTM4B）是一种新型的癌基因，可促进肿瘤发生，并且可能是几种癌症的潜在预后生物标志物。本研究旨在确定 LAPTM4B 在肺腺癌（LAC）中的临床意义和生物学作用。
采用免疫组织化学（IHC）检测 63 例 LAC 肿瘤中 LAPTM4B 的表达。采用酶联免疫吸附试验（ELISA）测定血清中 LAPTM4B 的水平。该研究包括未治疗组（n=216）、化疗组（n=29）、化疗有效组（n=179）、EGFR-TKIs 组（n=57）和 68 例健康对照组。进行统计学分析以探讨 LAPTM4B 表达与 LAC 临床病理参数之间的相关性。采用 Kaplan-Meier 分析评估 LAPTM4B 在 LAC 中的预后意义。进行体外实验以评估 LAPTM4B 在 LAC 细胞中的生物学作用。Western blot 实验检测鉴定 LAPTM4B 促进肿瘤发生的潜在通路。
我们发现 LAPTM4B 在 LAC 组织中上调，高表达与预后不良显著相关。化疗后血清 LAPTM4B 水平显著降低。无效反应组患者的 LAPTM4B 水平高于有效反应组。过表达 LAPTM4B 可促进 LAC 细胞的增殖、侵袭和迁移，而沉默 LAPTM4B 则抑制其增殖、侵袭和迁移，通过 PI3K/AKT 和 EMT 信号通路。LAPTM4B 的表达水平与表皮生长因子受体（EGFR）基因突变相关。此外，LAPTM4B 在 EGFR 促进的细胞增殖、迁移和侵袭以及吉非替尼诱导的细胞凋亡中发挥重要作用。
综上所述，我们的数据表明，LAPTM4B 可能是 LAC 的癌症生物标志物，也是一种潜在的治疗靶点，为开发针对 LAC 的新型治疗策略提供了依据。
