Relationship Between LAPTM4B Gene Polymorphism and Susceptibility of Malignant Melanoma in Chinese Patients

Lysosomal-associated protein transmembrane 4 beta (LAPTM4B) is known as an oncogene associated with many human malignant tumors. There are two alleles of the gene, LAPTM4B*1 and LAPTM4B*2. Previous studies have shown that LAPTM4B polymorphism contributes to the risk of many cancers. This case-control study was to investigate the relationship between LAPTM4B gene polymorphism and susceptibility of malignant melanoma. The genotypes of LAPTM4B were determined in 617 control subjects and 220 patients with malignant melanoma by utilizing polymerase chain reaction based on specific primers. The genotypic distribution of LAPTM4B and Hardy–Weinberg equilibrium were analyzed by χ2 test. Odds ratio and 95% confidence interval was calculated by unconditional logistic regression. The distributions of LAPTM4B genotypes were significantly different between melanoma patients (45.9% for *1/1, 46.4% for *1/2 and 7.7 for *2/2) and controls (54.5% for *1/1, 39.9% for *1/2 and 5.7 for *2/2). LAPTM4B *1/2 and LAPTM4B *2/2 had a 1.396-fold and 1.619-fold higher risk for melanoma occurrence than *1/1, and subjects with LAPTM4B*2 have a 1.308-fold higher risk than LAPTM4B*1 carriers. No association between LAPTM4B genotypes and gender, age, subtype, Clark level of invasion, Breslow thickness, ulceration, clinical stage, and C-KIT, BRAF gene mutation status was observed. LAPTM4B*2 is associated with the high risk of malignant melanoma and carrying LAPTM4B *2 may be a susceptible factor to Chinese melanoma patients

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

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).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.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.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

Association between LAPTM4B-35 expression and clinicopathological features of patients with gastric carcinoma in testing cohort.

<p>LAPTM4B: Lysosomal-associated protein transmembrane-4 beta</p><p>#: Pearson chi-square test</p><p>*: Fisher’s exact test</p><p>Association between LAPTM4B-35 expression and clinicopathological features of patients with gastric carcinoma in testing cohort.</p

Multivariate analysis of the prognostic factors in patients with gastric carcinoma by Cox proportional hazard model in testing cohort.

<p>LAPTM4B: Lysosomal-associated protein transmembrane-4 beta</p><p>B: coefficient; SE: standard error; RR: relative risk; CI: confidence interval</p><p>#: Cox regression test.</p><p>Multivariate analysis of the prognostic factors in patients with gastric carcinoma by Cox proportional hazard model in testing cohort.</p

Multivariate analysis of the prognostic factors in patients with gastric carcinoma by Cox proportional hazard model in discovery cohort.

<p>LAPTM4B: Lysosomal-associated protein transmembrane-4 beta</p><p>B: coefficient; SE: standard error; RR: relative risk; CI: confidence interval</p><p>#: Cox regression test.</p><p>Multivariate analysis of the prognostic factors in patients with gastric carcinoma by Cox proportional hazard model in discovery cohort.</p

Expression of LAPTM4B-35 in normal gastric mucosa, CAG, IM, IM beside GC, dysplasia and gastric carcinoma.

<p>#: Linear-by-Linear Association chi-square test</p><p>CAG: Chronic atrophic gastritis without intestinal metaplasia and dysplasia; IM: Intestinal metaplasia; GC: Gastric carcinoma.</p><p>LAPTM4B: Lysosomal-associated protein transmembrane-4 beta</p><p>Expression of LAPTM4B-35 in normal gastric mucosa, CAG, IM, IM beside GC, dysplasia and gastric carcinoma.</p

Association between LAPTM4B-35 expression and clinicopathological features of patients with gastric carcinoma in discovery cohort.

<p>LAPTM4B: Lysosomal-associated protein transmembrane-4 beta</p><p>#: Pearson chi-square test</p><p>*: Fisher’s exact test.</p><p>Association between LAPTM4B-35 expression and clinicopathological features of patients with gastric carcinoma in discovery cohort.</p

LAPTM4B-35 expression in gastric carcinoma tissues by Western blotting analysis.

<p>Protein samples obtained from frozen gastric carcinomas were analyzed by SDS-PAGE followed by immunoblotting with LAPTM4B-N1–99-pAb. In all samples, LAPTM4B-35 protein was detected as an approximately 35-kD band (upper panel). The levels of β tubulin were used as an internal control (lower panel).</p

LAPTM4B-35 expression in normal gastric mucosa, precancerous gastric lesions and gastric carcinoma by immunohistochemical staining.

<p>(A) Normal gastric mucosa (score: 0+0, negative). (B) Chronic atrophic gastritis without intestinal metaplasia and dysplasia (score: 0+0, negative). (C) Intestinal metaplasia (score: 1+2, positive). (D) Dysplasia (score: 1+2, positive). (E) Moderate differentiated gastric carcinoma (score: 1+2, positive). (F) Poorly differentiated gastric carcinoma (score: 2+2, positive). Original magnification, ×200.</p