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

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 conclusions were got that LAPTM4B-35 was an independent prognostic factor in a wide range of carcinomas [7-19]. LAPTM4B-35 was over-expressed in most human malignant tumors and precancerous lesions. Hence, we believed that LAPTM4B played important roles in the initiation, progression and metastasis of tumors. In fact, many researchs provide various markers in blood or body tissues for diagnosis, prognosis and therapeutics of GC. Such as CD133 [32], matrix metalloproteinase-9 [33], c-Met[34], et al. We hope to generate accurate diagnoses, prognoses and select the most appropriate therapy based on the markers. However, there are no current excellent markers for GC. Determining the significance of the markers requires an accumulation of practice. Recent studies showed that LAPTM4B had critical roles in multidrug resistance (MDR) via increasing drug efflux by P-glycoprotein (P-gp) to reduce drug concentration in cytoplasm and entry into nucleus, decreasing drug-induced DNA damage and escaping from drug-induced apoptosis [35, 36]. It was therefore possible that LAPTM4B-35-knockdown by RNAi may provide a promising novel therapy strategy in LAPTM4B-35 over-expression GC or other cancers. Recent studies showed that there were two alleles of the LAPTM4B gene, named as LAPTM4B^∗1 and LAPTM4B^∗2. The allele ^∗2 of LAPTM4B was found to be the risk factor of the certain tumors, such as breast carcinoma [37], colon carcinoma [38], hepatocellular carcinoma[39] and gastric carcinoma [40], and LAPTM4B ^∗2 was associated with poor prognosis of breast carcinoma [37], colon carcinoma [38] and hepatocellular carcinoma[39]. Although the exact molecular mechanisms underlying the function of LAPTM4B in carcinogenesis had not as yet been worked out, LAPTM4B^∗2 may be an oncogene or play an important role in cell cycle control. Therefore, further elucidation of the role of LAPTM4B gene in the GC will require genotyping in additional samples in the future studies. In conclusion, the present research demonstrated that LAPTM4B-35 was over-expressed in a large proportion of patients with precancerous gastric lesions or GC. There were steadily increasing expression of LAPTM4B-35 in series of precancerous gastric lesions. And a close association between LAPTM4B-35 over-expression and disease progression, poor prognosis in GC was found for the first time. These findings suggested that LAPTM4B may be a useful and critical molecular marker to predict the progression of precancerous gastric lesions and the prognosis of patients with GC. LAPTM4B gene may provide a useful target of interventions slowing the progression of precancerous gastric lesions and a new therapy method to improve the prognosis of patients with GC.