LAPTM4B Allele *2 Is a Marker of Poor Prognosis for Gallbladder Carcinoma

Guojun Zhai,Jiuling Yang,Hua Yang,Fuxia Xiong,Jing Su,Wenrui Xu,Kaowen Yan,Xiaoxu Ji,Michael A Mcnutt,Alejandro H Corvalan

doi:10.1371/journal.pone.0045290

Guojun Zhai, Jiuling Yang + Show 8 more

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https://doi.org/10.1371/journal.pone.0045290

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Abstract

BackgroundLysosomal protein transmembrane 4 beta (LAPTM4B) is a novel cancer-related gene which has two alleles designated LAPTM4B*1 and LAPTM4B*2. In this study we investigated the correlation of LAPTM4B genotype with prognosis and clinicopathologic features in patients who had undergone curative resection for gallbladder carcinoma (GBC).Methodology/Principal FindingsPCR assay was performed to determine the LAPTM4B genotype in 85 patients. The correlation of LAPTM4B genotype with clinicopathologic parameters was assessed with the Chi-squared test. Differences in patient survival were determined by the Kaplan–Meier method. Multivariate analysis of prognostic factors was carried out with Cox regression analysis. Patients with LAPTM4B *2 had both significantly shorter overall survival (OS) and shorter disease-free survival (DFS) (both P<0.001). Multivariate analysis showed that LAPTM4B genotype is a prognostic factor for OS and DFS (both P<0.001).Conclusions/SignificanceLAPTM4B allele *2 is a risk factor associated with poor prognosis in patients with resected GBC, and LAPTM4B status may be therefore be useful preoperatively as an adjunct in evaluation of the operability of GBC.

Highlights

Gallbladder carcinoma (GBC) is a highly aggressive neoplasm with a poor prognosis [1], and it is the fifth most common tumor of the digestive tract [2]
We found that genotype *2 of the Lysosomal protein transmembrane 4 beta (LAPTM4B) gene was significantly associated with poor histopathologic differentiation, higher TNM stage and lymph node metastasis (Table 1; P,0.05), but not with age, gender, or tumor size (Table 1; P.0.05)
We tested for LAPTM4B genotype by PCR assay in 85 patients who had surgical resection for gallbladder carcinoma

Summary

Introduction

Gallbladder carcinoma (GBC) is a highly aggressive neoplasm with a poor prognosis [1], and it is the fifth most common tumor of the digestive tract [2]. It has been reported that LAPTM4B protein is significantly up-regulated in a wide variety of cancers including hepatocellular carcinoma, extrahepatic cholangiocarcinoma, breast cancer, endometrial carcinoma, cervival carcinoma and ovarian cancer as well as gallbladder carcinoma. This overexpression is significantly correlated with prognosis [8,9,10,11,12,13,14,15,16]. In this study we investigated the correlation of LAPTM4B genotype with prognosis and clinicopathologic features in patients who had undergone curative resection for gallbladder carcinoma (GBC)

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