Abstract
BackgroundLysosome-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.MethodsIn 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.ResultsIHC 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).ConclusionThese 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.
Highlights
Gastric cancer is the third most common cancer in China and the leading cause of cancer-related death in China [1]
Multivariate analysis showed high expression of Lysosome-associated protein transmembrane 4 beta (LAPTM4B)-35 was an independent prognostic factor for overall survival (OS) in stage I-III gastric cancer (GC) patients (P = 0.025). These findings indicate that LAPTM4B-35 overexpression may be related to GC progression and poor prognosis, and may serve as a new prediction marker of prognosis in GC patients
We firstly examined the expression of LAPTM4B-35 by RT-PCR in 5 GC cell lines (MGC-803, BGC-823, MKN-28, SGC-7901 and AGS), and detected its protein expression by Western blot
Summary
Gastric cancer is the third most common cancer in China and the leading cause of cancer-related death in China [1]. Lysosome-associated protein transmembrane 4 beta (LAPTM4B) has been originally cloned in hepatocellular carcinomas (HCCs) by Shao et al, which located at chromosome 8q22, a region frequently amplified in breast cancer and HCC [10, 11]. It encodes two proteins with different molecular weight, 24-kDa and 35-kDa proteins (LAPTM4B-24 and -35) with four putative transmembrane regions [12]. 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
Published Version (Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have