55353

LAPTM4B

lysosomal protein transmembrane 4 beta;LAPTM4B;lysosomal protein transmembrane 4 beta

lysosomal associated protein transmembrane 4 beta|lysosomal-associated transmembrane protein 4B|lysosome-associated transmembrane protein 4-beta

8q22.1

protein-coding

PURPOSE: Lysosome-associated protein transmembrane 4 beta (LAPTM4B), a novel oncoprotein, has been shown to be overexpressed in several human malignancies. Our purpose was to evaluate the expression of LAPTM4B in breast carcinoma and its significance, which was not previously studied by others. METHODS: Through immunohistochemistry, LAPTM4B expression was evaluated in 35 benign breast tumor specimens and 194 breast cancer specimens. The correlation of LAPTM4B expression with clinicopathological parameters was assessed using chi(2) analysis. The survival status of patients was analyzed using the Kaplan-Meier and log-rank tests. Cox regression was used for the multivariate analysis of prognostic factors. RESULTS: The immunohistochemistry results showed that the expression level of LAPTM4B in breast cancer cases was significantly higher than that in benign breast tumor tissues (P < 0.001). Moreover, statistical analysis also showed that high LAPTM4B expression was positively related to TNM stage, lymph node metastasis, and recurrence. Furthermore, it was also shown that patients with high LAPTM4B expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of LAPTM4B (P = 0.019 and P = 0.005, respectively). Multivariate Cox regression analysis revealed that high LAPTM4B expression level was an independent prognostic factor for both overall survival and disease-free survival of patients with breast cancer (P = 0.041 and P = 0.023, respectively). CONCLUSIONS: Overexpression of LAPTM4B may contribute to the tumor progression and poor prognosis of breast cancer, thus testing the expression of LAPTM4B will be helpful for predicting prognosis in breast cancer.

PURPOSE: Lysosomal protein transmembrane 4 beta-35 (LAPTM4B-35) is a tetra-transmembrane glycoprotein that is abundantly localized on membrane-bound organelles including endosomes and lysosomes, and promotes cell proliferation and tumorigenesis through regulation of cell cycle and signaling pathways. The aim of the present study is to determine the potential clinical implications of LAPTM4B-35 expression in hepatocellular carcinoma (HCC). METHODS: Immunohistochemistry assay was used to determine the expression of LAPTM4B-35 protein in normal and HCC tissues from 71 patients. The correlations of LAPTM4B-35 expression with clinicopathological parameters, including gender, age, background liver, viral status, tumor size, portal vein invasion, histopathological differentiation, serum AFP level, TNM staging and recurrence of HCC were assessed by Chi-squared test. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. Cox regression (Proportional hazard model) was adopted for multivariate analysis of prognostic factors. RESULTS: LAPTM4B-35 immunoreactivity was negative or low in normal liver tissues, but high in HCC tissues (51/71, 71.8%). The overexpression of LAPTM4B-35 was significantly associated with recurrence, TNM staging and portal vein invasion of HCC. Patients with high LAPTM4B-35 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001) when compared with patients with the low expression of LAPTM4B-35. On multivariate analysis, LAPTM4B-35 expression was found to be an independent prognostic factor for OS and DFS (P = 0.018 and P = 0.001, respectively). CONCLUSION: LAPTM4B-35 expression showed a strong association with the potencies of recurrence and metastasis and progression of HCC, and that may be applied as a novel marker for the prediction of recurrence and metastasis potency of HCC, and helpful for improving the diagnosis, prognosis and treatment of HCC.

Lysosomal protein transmembrane 4 beta (LAPTM4B) was originally identified as a hepatocellular carcinoma (HCC)-associated gene. This gene and its protein product LAPTM4B-35, are both overexpressed in a variety of human cancers. However, its specific role in cell transformation and malignancy has remained elusive. In the present study we investigated the effects of LAPTM4B-35 overexpression on the malignant phenotypic features in the HLE cell line. Our data show that overexpression of LAPTM4B-35 promotes cell proliferation, exogenous growth-stimulating factor-independent and anchorage-independent growth, and enhances metastatic potential, including promotion of both cell migration and invasion. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included upregulation of proliferation-promoting transcription factors such as c-Myc, c-Jun, and c-Fos, and cell cycle-promoting proteins such as cyclin D1 and cyclin E. In addition, mutagenesis study showed that the PPRP motif in the N-terminal region of LAPTM4B-35 plays a critical role in promoting proliferation, migration, and invasion, as well as in the upregulation of the oncoproteins noted above. These data offer insight into the mechanism by which this novel tetratransmembrane protein contributes to the pathogenesis of liver cancer, and suggest that it may be a potential target for cancer therapy.

OBJECTIVE: metastatic ovarian tumors are a series of lethal carcinomas that almost always have bad prognosis. Their prognoses, however, vary depending on the primary tumor malignancies of each. It has been reported that LAPTM4B, a novel tumor-associated gene, might indicate a worse prognosis when it was overexpressed in other carcinomas. Therefore, the authors expected to investigate whether LAPTM4B overexpression is an independent prognostic marker in metastatic ovarian tumors. METHODS: Immunohistochemistry was used to assess LAPTM4B expression in metastatic ovarian tumors from 102 patients. Subsequently, univariate and multivariate survival analyses with Cox regression were performed to determine the association between LAPTM4B expression and prognosis. To identify any differences in prognosis between the 2 groups of patients with differing primary malignancies, the log-rank test was used. RESULTS: The median overall and progression-free survival rates of patients with tumors of gastrointestinal tract origin were 0.97 and 0.51 years, respectively, and both were statistically significantly lower than those of patients with tumors of breast origin (P < 0.0001), which were 2.68 and 1.96 years, accordingly. Of 102 patients, 77 were classified as having a high expression of LAPTM4B, and LAPTM4B expression had a significant association with the prognosis of metastatic ovarian tumors (P < 0.01); no statistically significant interaction between LAPTM4B expression and primary malignancies was detected (P > 0.1). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001). CONCLUSIONS: Patients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the disease from gastrointestinal tract primary malignancies. LAPTM4B overexpression might be an independent prognostic marker of metastatic ovarian tumors.