Lysosomal-associated protein transmembrane 4 Beta-35 overexpression is a novel independent prognostic marker for gastric carcinoma

PLoS One. 2015 Feb 17;10(2):e0118026. doi: 10.1371/journal.pone.0118026. eCollection 2015.

Abstract

Objective: The purpose of this work was to analyze the relationships between the expression status of Lysosomal-associated protein transmembrane-4 beta 35 (LAPTM4B-35) in cancerous tissues and clinicopathological characteristics and prognosis of the patients with gastric carcinoma (GC).

Methods: The GC samples from 157 patients in a discovery cohort and 148 patients in a testing cohort with follow-up data were used to validate the feasibility of expression of LAPTM4B-35 protein in predicting GC prognosis. Immunohistochemical staining was used to determine the expression of LAPTM4B-35 protein in precancerous gastric lesions and gastric carcinomas. The correlation between the expression of LAPTM4B-35 and clinicopathologic characteristics of patients with gastric carcinoma was analyzed using chi-square test. Univariate and multivariate analyses were performed to determine the association between LAPTM4B-35 expression and prognosis.

Results: LAPTM4B-35 expression was increased steadily in sequential stages of precancerous gastric lesions. Positive LAPTM4B-35 expression was more frequently detected in patients with distant metastasis (P = 0.023) and III+IV TNM stages (P = 0.042) in the discovery cohort. Kaplan-Meier survival curves and univariate analysis showed that expression of LAPTM4B-35 had a significant impact on overall survival of patients with gastric carcinoma in discovery cohort (P<0.001) and testing cohort (P = 0.001). LAPTM4B-35 expression was an independent prognostic indicator for the overall survival of patients with gastric carcinoma in both cohorts.

Conclusions: The present research demonstrated that LAPTM4B-35 over-expression was an independent factor in gastric carcinoma prognosis. LAPTM4B gene may be a useful target of interventions slowing the progression of precancerous gastric lesions and a new therapy method to improve the prognosis of gastric carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Female
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastritis, Atrophic / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Membrane Proteins / metabolism*
  • Metaplasia
  • Middle Aged
  • Oncogene Proteins / metabolism*
  • Prognosis
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • LAPTM4B protein, human
  • Membrane Proteins
  • Oncogene Proteins

Grants and funding

This work was supported by grants from the Natural Science Foundation of Shandong Province (No. ZR2011HM073 and No. ZR2011HQ025, http://www.sdnsf.gov.cn/portal/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.