Abstract
BackgroundLysosomal-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).MethodsLAPTM4B 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.ResultsWe 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.ConclusionsCollectively, 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.
Highlights
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B), a novel oncogene, promotes tumorigenesis and may be a potential prognostic biomarker in several cancers
The expression of LAPTM4B in lung adenocarcinoma (LAC) tissues and correlation with prognosis We first analyzed LAPTM4B mRNA expression levels in LAC tissue from TCGA (The Cancer Genome Atlas) database and revealed that LAPTM4B was upregulated in LAC tissues compared with normal tissue samples (Fig. 1a)
The expression levels of LAPTM4B were positively correlated with advanced clinical stages, lymph node metastasis and epidermal growth factor receptor (EGFR) mutations
Summary
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). Lung adenocarcinoma (LAC) is currently the main histological subtype of NSCLC and the average 5-year survival rate of NSCLC patients remains lower than 15% [2]. The widely used diagnostic markers for lung cancer are pro-gastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment (CYFRA21-1) [4]. These tumor markers display relatively low sensitivity and specificity, so their clinical applications are limited [5, 6]. It is crucial for identification of new targets for diagnosis and monitoring treatment
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