LAPTM4B Research Articles

A Game-Theoretical Approach to Clinical Decision Making with Immersive Visualisation

Cancer is a disease characterised by changes in combinations of genes within affected tumour cells. The deep understanding of genetic activity afforded to cancer specialists through complex genomics data analytics has advanced the clinical management of cancer by using deep machine learning algorithms and visualisation. However, most of the existing works do not integrate intelligent decision-making aids that can guide users in the analysis and exploration processes. This paper contributes a novel strategy that applies game theory within a VR-enabled immersive visualisation system designed as the decision support engine to mimic real-world interactions between stakeholders within complex relationships, in this case cancer clinicians. Our focus is to apply game theory to assist doctors in the decision-making process regarding the treatment options for rare-cancer patients. Nash Equilibrium and Social Optimality strategy profiles were used to facilitate complex analysis within the visualisation by inspecting which combination of genes and dimensionality reduction methods yields the best survival rate and by investigating the treatment protocol to form new hypotheses. Using a case simulation, we demonstrate the effectiveness of game theory in guiding the analyst with a patient cohort data interrogation system as compared to an analyst without a decision support system. Particularly, the strategy profile (t-SNE method and DNMT3B_ZBTB46_LAPTM4B gene) gains the highest payoff for the two doctors.

Autophagy-related gene LAPTM4B promotes the progression of renal clear cell carcinoma and is associated with immunity.

Renal cell carcinoma (RCC) is a common urologic disease. Currently, surgery is the primary treatment for renal cancer; immunotherapy is not as effective a treatment strategy as expected. Hence, understanding the mechanism in the tumor immune microenvironment (TME) and exploring novel immunotherapeutic targets are considered important. Recent studies have demonstrated that autophagy could affect the immune environment of renal cell carcinoma and induce proliferation and apoptosis of cancer cells. By comparing lysosomal genes and regulating autophagy genes, we identified the LAPTM4B gene to be related to RCC autophagy. By analyzing the TCGA-KIRC cohort using bioinformatics, we found M2 macrophages associated with tumor metastasis to be significantly increased in the immune microenvironment of patients with high expression of LAPTM4B. GO/KEGG/GSEA/GSVA results showed significant differences in tumor autophagy- and metastasis-related pathways. Single-cell sequencing was used to compare the expression of LAPTM4B in different cell types and obtain the differences in lysosomal and autophagy pathway activities in different ccRCC cells. Subsequently, we confirmed the differential expression of LAPTM4B in renal cell carcinoma of different Fuhrman grades using western blotting. Downregulation of LAPTM4B expression significantly reduced the proliferation of renal cell carcinoma cells and promoted cell apoptosis through cell experiments. Overall, our study demonstrated that the autophagy-related gene LAPTM4B plays a critical role in the TME of RCC, and suggested that LAPTM4B is a potential therapeutic target for RCC immunotherapy.

SNHG16 promotes cell proliferation and migration through sponging miR-132 in melanoma.

Melanoma, which originates from the transformation of normal melanocytes, is one of the three main types of skin cancer. We aimed to explore the functions of SNHG16 and miR-132 in melanoma. CCK-8, Transwell assays were used to measure the viability and migration, respectively. Spearman's correlation analysis was performed to analyze the relationship between the expression of SNHG16, miR-132 and LAPTM4B in melanoma tissues. SNHG16 was overexpressed, and miR-132 was low expressed in melanoma tissues and cell lines. Moreover, overexpression of SNHG16 was associated with poor prognosis of melanoma patients. The expression of SNHG16 had a negative connection with the expression of miR-132, and it had a positive relationship with the expression of LAPTM4B in melanoma tissues. Knockdown of SNHG16 or overexpression of miR-132 inhibited SK-MEL-2 cell proliferation and migration. In addition, we confirmed that SNHG16 directly binding to miR-132 promotes the expression of LAPTM4B, facilitating the tumorigenesis of melanoma. SNHG16 promotes the expression of LAPTM4B by sponging miR-132, thereby acting as an oncogene in melanoma. This study demonstrated that the lncRNA-miRNA-mRNA signal cascade existed in melanoma, which may help elucidate the tumorigenesis and development mechanism of melanoma.

Assocition between LAPTM4B gene polymorphism and the risk of childhood acute lymphoblastic leukemia

Assocition between LAPTM4B gene polymorphism and the risk of childhood acute lymphoblastic leukemia

Investigation into the underlying molecular mechanisms of non-small cell lung cancer using bioinformatics analysis

Development of new therapeutic strategies has proven to be of little impact on non-small cell lung cancer (NSCLC), and unfortunately, its molecular mechanisms still remain poorly understood. Therefore, the current study aimed to diagnose the genes associated in the pathogenesis of NSCLC. The differentially expressed genes (DEGs) were diagnosed using the limma software package. The WebGestalt was used to perform pathway and Gene Ontology (GO) enrichment analysis of the DEGs. Protein-protein interaction (PPI) networks, extracted modules, miRNA-target genes regulatory network and miRNA-target genes regulatory network were used to obtain insight into the actions of DEGs. Survival analysis for DEGs carried out. A total of 118 DEGs, including 74 up-regulated and 44 down-regulated genes were diagnosed between serum starved Calu-6 lung cancer cells transfected with control siRNA and serum starved Calu-6 lung cancer cells transfected with siRNA against the LAPTM4B gene. The up-regulated genes were enriched in PPAR signalling pathway, angiogenesis, positive regulation of neuron projection development and extracellular space. The down-regulated genes were enriched in FoxO signalling pathway, plasminogen activating cascade, cardiac chamber morphogenesis and cell surface. The current study screened the genes in PPI network, extracted modules, miRNA-target genes regulatory network and TF-target genes regulatory network with higher degrees as hub genes, which included FGFR1, HEY1, SPP1, FOS, NDRG1, TFF3, CDK15, PDGFRB, IL7R, LYPD6B, IQGAP2, CEACAM1, VEGFA, SGK1, GPRC5B and WNT5A. Survival and expression analysis suggested that low expressed CACNA1C and GATA2, and high expressed MANSC1 and MSX2 in patients with NCSLC was linked with a positive prognosis for overall survival and all individual stages of NSCLC. In conclusion, the current study diagnosed DEGs between serum starved Calu-6 lung cancer cells transfected with control siRNA and serum starved Calu-6 lung cancer cells transfected with siRNA against the LAPTM4B gene, which could improve our understanding of the molecular mechanisms of small interference RNA (siRNA) against LAPTM4B in NSCLC, and up- and down-regulated genes, over and under expressed genes in NSCLC patients indicated a positive prognosis for overall survival and may be used as a prognostic biomarker for patients with NSCLC. Thus, we developed a signature based on seven DEGs with prognostic value for NSCLC patients using multi-steps bioinformatics methods, which may provide new insights and potential biomarkers for prognosis, as well as possibly serving as new therapeutic targets in clinical applications.

LAPTM4B gene copy number gain is associated with inferior response to anthracycline-based chemotherapy in hormone receptor negative breast carcinomas.

To determine the associations between lysosomal-associated transmembrane protein 4b (LAPTM4B) gene copy number and response to different chemotherapy regimens in hormone receptor negative (HR-) primary breast carcinomas. Two cohorts were analyzed: (1) 69 core biopsies from HR-breast carcinomas treated with neoadjuvant chemotherapy (anthracycline based in 72.5% of patients and non-anthracycline based in 27.5% of patients). (2) Tissue microarray (TMA) of 74 HR-breast carcinomas treated with adjuvant therapy (77.0% of the patients received anthracycline, 17.6% of the patients non-anthracycline-based therapy, and in 5.4% of the cases, no treatment data are available). Interphase FISH technique was applied on pretreatment core biopsies (cohort I) and on TMAs (cohort II) using custom-made dual-labelled FISH probes (LAPTM4B/CEN8q FISH probe Abnova Corp.). In the neoadjuvant cohort in the anthracycline-treated group, we observed a significant difference (p = 0.029) of average LAPTM4B copy number between the non-responder and pathological complete responder groups (4.1 ± 1.1 vs. 2.6 ± 0.1). In the adjuvant setting, the anthracycline-treated group of metastatic breast carcinomas was characterized by higher LAPTM4B copy number comparing to the non-metastatic ones (p = 0.046). In contrast, in the non-anthracycline-treated group of patients, we did not find any LAPTM4B gene copy number differences between responder vs. non-responder groups or between metastatic vs. non-metastatic groups. Our results confirm the possible role of the LAPTM4B gene in anthracycline resistance in HR- breast cancer. Analyzing LAPTM4B copy number pattern may support future treatment decision.

Association between LAPTM4B gene polymorphism and susceptibility to and prognosis of diffuse large B-cell lymphoma.

Lysosomal protein transmembrane 4β (LAPTM4B) is an oncogene that is overexpressed in a number of various types of human cancer. There are two known alleles of LAPTM4B: LAPTM4B*1 and LAPTM4B*2. The present study assessed the association between LAPTM4B polymorphisms and the susceptibility to diffuse large B-cell lymphoma (DLBCL) and its prognosis. LAPTM4B genotypes were determined using polymerase chain reaction analysis in 164 DLBCL and 350 healthy control cases. The association between LAPTM4B polymorphisms and the risk of DLBCL was analyzed using unconditional logistic regression. Differences in patient survival were calculated using Kaplan-Meier analysis. The present study indicated no significant differences (P>0.05) in the frequency of LAPTM4B*2 alleles between DLBCL cases (26.5%) and controls (24.1%). The risk of DLBCL was slightly increased in cases with the LAPTM4B*1/2 genotype [odds ratio (OR)=1.160; 95% confidence interval (CI)=0.781–1.724] or the LAPTM4B*2/2 genotype (OR=1.446; 95% CI=0.648–3.227) compared with those with the LAPTM4B*1/1 genotype. There was no significant association between the presence of the LAPTM4B*2 allele and overall survival (OS) and disease-free survival (DFS) in patients with DLBCL (P=0.399 and 0.520, respectively). However, there was a tendency for patients with LAPTM4B*2 and International Prognostic Index (IPI) score 3–5 to have longer OS and DFS (P=0.126 and 0.109, respectively). These findings suggest that genetic polymorphisms of LAPTM4B is not a risk factor for the development of DLBCL, but the LAPTM4B*2 allele may a better prognostic indicator in patients with IPI score 3–5 in DLBCL.

LAPTM4B*2 allele is associated with the development of papillary thyroid carcinoma in Chinese women.

Lysosome-associated protein transmembrane 4-β (LAPTM4B) contains a polymorphic region that contributes to the increased risk of numerous types of tumor. However, no study has yet demonstrated an association between the expression of the LAPTM4B gene and tumor differentiation, and the reason that LAPTM4B polymorphisms affect the susceptibility of individuals to cancer remains to be elucidated. The present study assessed the possible association between LAPTM4B polymorphism and the risk of papillary thyroid carcinoma (PTC), and attempted to identify the underlying mechanism for variation in patient susceptibility with respect to transcription regulation in the polymorphism region. The case control study included 183 papillary thyroid carcinoma patients (132 females, 51 males) and 697 healthy controls (249 females, 448 males). Genomic DNA was extracted from the blood and the genotype of LAPTM4B was identified using polymerase chain reaction (PCR). The results of the PCR revealed that LAPTM4B allele *2 was associated with PTC risk in comparison with LAPTM4B allele *1 [odds ratio (OR), 1.968; 95% confidence interval (CI), 1.363–2.841, P<0.001] in females, while LAPTM4B*2 was not associated with PTC risk in males (OR, 0.996, 95% CI, 0.615–1.612, P=0.986). Notably, LAPTM4B polymorphism was not associated with clinical parameters in the female patient group. In addition, by performing a luciferase reporter assay in the PTC TPC1 and B-CPAP cell lines, the transcriptional activity of the +10/+311 plasmid, representing LAPTM4B*2 was reduced compared with that of the +10/+292 plasmid representing LAPTM4B*1. In conclusion, the results of the present study suggested that LAPTM4B*2 was a susceptibility factor for PTC in the female Chinese population and this may not be caused by the transcriptional regulation of LAPTM4B polymorphism region in TPC1 and B-CPAP cell lines.

Relationship between LAPTM4B Gene Polymorphism and Prognosis of Patients following Tumor Resection for Colorectal and Esophageal Cancers.

BackgroundLysosome-associated transmembrane-4 beta (LAPTM4B) is an oncogene that participates tumorgenesis in a variety of human solid tumors, and it has two alleles named as LAPTM4B*1 and *2. The present study aimed to identify the association of LAPTM4B genotype with clinicopathological features and prognosis in colorectal and esophageal cancer patients.MethodGenotypes of LAPTM4B were determined by PCR in 167 colon cancer cases (72 patients in a discovery cohort and 95 patients in a testing cohort), 160 rectal cancer cases and 164 esophageal cancer cases. Association between the LAPTM4B gene polymorphism and clinicopathological variables was calculated by Chi-square test or Fisher’s exact test. Patient survival differences were calculated by the Kaplan-Meier method. Prognostic factors were determined with Log-rank test and Cox regression model.ResultsLAPTM4B *1/1 was more frequently detected in colon cancer patients with lymph node metastasis and TNM III+IV stages in total colon cancer (discovery + testing cohorts). LAPTM4B *2/2 decreased in recurrent patients in total colon cancer patients (P = 0.045). Kaplan-Meier survival curves and Log-rank test showed that LAPTM4B*1 was correlated with shorter overall survival (OS) in discovery and testing cohorts of colon cancer (P = 0.0254 and 0.0292, respectively), but not in rectal and esophageal cancer cases (P = 0.7669 and 0.9356, respectively). Multivariate analysis showed that LAPTM4B genotype was an independent prognostic factor for OS in total colon cancer [P = 0.004, hazard ratio (HR) = 0.432; 95% confidence interval (CI) = 0.243–0.768], but not in rectal and esophageal cancers (P = 0.791, HR = 1.073, 95% CI = 0.638–1.804 and 0.998, HR = 1.000, 95% CI = 0.663–1.530, respectively).ConclusionThese findings suggested that LAPTM4B allele *1 was a risk factor associated with poor prognosis in patients with colon cancer, but not in patients with rectal or esophageal cancers. LAPTM4B genotype status might be a useful prognostic indicator for patients that need surgical operation in colon cancer.

Association between LAPTM4B gene polymorphism and prostate cancer susceptibility in an Iranian population

ABSTRACTLysosome associated protein transmembrane 4 β (LAPTM4B) is an oncogene associated with many human cancers. In the present study we aimed to examine the possible association between LAPTM4B polymorphism and risk of prostate cancer (PCa) in an Iranian population. This case control study was performed on 168 patients with PCa and 176 controls with benign prostatic hyperplasia (BPH). Genomic DNA was extracted from whole blood and LAPTM4B genotypes were identified by polymerase chain reaction. The distributions of LAPTM4B genotypes were significantly different between PCa patients (60.7% for *1/1, 32.8% for *1/2, and 6.5% for *2/2) and controls (44.9% for *1/1, 49.4% for *1/2, and 5.7% for *2/2). Both the *1/2 and *1/2+*2/2 genotypes significantly decreased the risk of PCa compared with the *1/1 genotype (OR = 49, 95% CI = 0.31–0.77, p = 0.002 and OR = 0.53, 95% CI = 0.34–0.81, p = 0.004, respectively). The minor allele (LAPTM4B*2) was associated with a decreased risk of PCa compared with the LAPTM4B*1 allele (OR = 0.68, 95% CI = 0.48–0.96, p = 0.031). Moreover, LAPTM4B polymorphism was not associated with clinicopathological characteristics of PCa patients. The results of this study showed that LAPTM4B*2 was associated with a decreased risk of PCa but the clinicopathological characteristics of PCa were not linked to LAPTM4B polymorphism. Further studies with larger sample sizes and different ethnicities are needed to confirm our findings.

LAPTM4B Gene Expression and Polymorphism as Diagnostic Markers of Breast Cancer in Egyptian Patients.

SummaryBackgroundThe aim of this study was to investigate the association between LAPTM4B gene polymorphism and the risk of breast cancer among Egyptian female patients. Also, measurement was done of its serum level to evaluate its significance as a diagnostic marker for breast cancer.MethodsThis case control study was done on 88 breast cancer patients, 40 with fibroadenoma and 80 healthy subjects. Genotyping of the LAPTM4B polymorphism was determined by PCR. Serum LAPTM4B level was measured using ELISA.ResultsThere was a significant difference in the (*1/2+ *2/2) genotypes in breast cancer patients (59.1) compared to the control subjects (43.8%) (P=0.047; OR=1.86; 95% CI =1.01–3.43). The frequency of the allele 2* of the LAPTM4B gene was significantly higher in breast cancer patients (36.4%) than in the control (25.6%) (p=0.034; OR=1.66; 95% CI =1.04–2.65). Genotypes (*1/2+*2/2) were significantly associated with the differential classification of TNM. Serum level of LAPTM4B was significantly higher in breast cancer patients than in control and fibroadenoma and in fibroadenoma patients than in control. In breast cancer patients, serum LAPTM4B was significantly higher in stage III and in large tumor size. Serum LAPTM4B was significantly higher in the cancer patients’ genotypes (*1/2+*2/2).ConclusionsGenetic polymorphism of LAPTM4B is a potential risk factor for the development of breast cancer. Serum LAPTM4B may be used as a diagnostic and prognostic marker for breast cancer.

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

ObjectiveThe 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).MethodsThe 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.ResultsLAPTM4B-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.ConclusionsThe 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.

Relationship between LAPTM4B gene polymorphism and susceptibility of primary liver cancer

Lysosome associated protein transmembrane 4 beta (LAPTM4B) was identified first as a novel gene overexpressed in human hepatocellular carcinoma. LAPTM4B*1 and LAPTM4B*2 are two alleles of the gene; they are differentiated at 5'UTR in the first exon. Allele *1 contains only one copy of a 19-bp sequence in the 5'UTR. However, allele *2 contains another identical 19-bp sequence following the first one tightly. In this case-control study, we aimed to identify the relationship between LAPTM4B gene polymorphism and the susceptibility of primary liver cancer. The case-control study was conducted in China, including 303 primary liver cancer cases and 515 controls. LAPTM4B gene polymorphism was determined by PCR. Statistical analysis includes odds ratio (OR) and 95% confidence interval (CI) calculations using unconditional logistic regression. We found a significant difference in the frequency of LAPTM4B*2 between cases and controls (P<0.05). Our study showed that LAPTM4B*1/2 and *2/2 were associated with a significantly increased risk of primary liver cancer compared with LAPTM4B*1/1 (OR=1.898, 95% CI=1.387-2.598 and OR=2.483, 95% CI=1.480-4.168, respectively). The genotypes of LAPTM4B in this study have negative correlation with the clinicopathologicals observed. The evidences suggest that gene polymorphism of LAPTM4B may influence the individuals' susceptibility to primary liver cancer and allele *2 being considered as a potential risk factor.

Association of LAPTM4B gene polymorphism with breast cancer susceptibility

BackgroundLysosome associated protein transmembrane 4 beta (LAPTM4B) was a cancer-associated gene that is mapped to chromosome 8q22 with seven exons and six introns. LAPTM4B gene polymorphism has been reported to be significantly associated with susceptibility of several solid tumors. MethodsWe performed a case-control study was to investigate the association between LAPTM4B polymorphism and the risk of breast cancer in 732 breast cancer patients and 649 controls. ResultsA significant difference in the frequency of LAPTM4B*2 was observed between the patients and the controls (P<0.01). Using the LAPTM4B*1/1 genotype as a reference, we found that LAPTM4B allelic variation was significantly associated with breast cancer occurrence, with adjusted odds ratios of 1.387 (95%CI=1.111–1.730) for LAPTM4B*1/2 and 1.592 (95% CI=1.043–2.430) for LAPTM4B*2/2 genotype. ConclusionOur results suggested that LAPTM4B*2 is associated with an increased risk of breast cancer in the Chinese women population and may be a risk factor of breast cancer.

Mutations and polymorphisms of genes moderate increase in gastric cancer risk

Results of studies performed in our center point at DNA changes of many cancer (mostly moderate) susceptibility genes. Association of weak mutations and polymorphism of many genes and additional influence of environmental factors can significantly increase the risk of cancer development. The preliminary studies performed in our department indicate, that increased risk of gastric cancer may be related to mutation in NOD2 and CHK2 genes predisposing to cancers of many organs. The CHEK2 gene encodes checkpoint kinase 2 (Chk2), it acts as a tumor suppressor whose functions are central to the induction of cell cycle arrest and apoptosis by DNA damage. Results of studies performed in our center indicate that the frequency of the IVS2+1G→A alteration was significantly increased in a group of 658 consecutive patients, especially in those under 50 years of age (OR=5.332, p=0.0174). I157T was over-represented in the group of familial gastric cancer patients, particularly in patients diagnosed at less than 50 years of age (OR=3.687, p=0.0011) and females. The specific group of intestinal and mixed histopathological subtype occurs more frequently (OR=1.671) in consecutive carriers of I157T mutation. Recently, the NOD2/CARD15, gene located on chromosome 16q12, has been associated with Crohn’s disease. It is believed to play a role both in intracellular recognition of lipopolysaccharides (LPS) typical of Gram negative bacteria and subsequent activation of NFkB. 3020insC NOD2 mutation causes an increased risk of developing chronic inflammatory diseases of the gastrointestinal tract and colorectal cancer in their course. In light of recent studies, in fact 3020insC mutation predisposes to cancers of many organs, including breast, ovarian, lung. Studies conducted in our center in the group of 103 patients with a family history of gastric cancer, have shown that NOD2 3020insC carriers in persons over 50 y of age more than doubled (OR=2.479, p=0.022) and among women almost 3-fold increased risk. In addition, NOD2 R702W alteration occurred almost three times more frequently (OR=2.816, p=0.0121) in the group of 241 consecutive patients with gastric cancer diagnosed before 50 years of age and over 2-times frequently (OR=2.268, p=0.0371) in gastric cancer selected histopathologically as intestinal type according to Lauren. There are a large number of reports describing the relationship between changes in the gene TP53, particularly polimomorfizm Arg72Pro, and risk of gastric cancer. Many researchers have found links between gene polymorphism of Interleukin-1, and the risk of stomach cancer. Gene polymorphism of angiotensin converting enzyme ACE, was recently linked with the pathogenesis and development of human cancers. Research Ebert MP, et al. conducted in a group of 88 patients shows that the insertion / deletion ACE gene may be associated with the development of early gastric cancer in the German population. In the Japanese population genetically distant, however, found no relationship between gastric cancer and ACE gene polymorphism). Sentences on the ACE polymorphism and risk of stomach cancer researchers are divided among different centers. XRCC1 gene is part of composite protein complex containing the s-polymerase DNA ligase I and PARP (polymerase poly (ADP-ribose). This multi-unit complex is involved in DNA repair pathway. T. Poplawski et al. indicate that the variant Gln / Gln XRCC1 gene polymorphism Arg399Gly occurred more frequently in patients with gastric cancer and family burden (OR=2.04, 95% CI=1,27-3,29) and the results obtained from studies in the group of 152 patients with a family history of gastric cancer suggest that gene XRCC1 399Gln allele may be considered a marker of gastric cancer. In terms of predisposition to gastric cancer has also been studied recently LAPTM4B gene associated with a genetic predisposition to liver cancer, having LAPTM4B alleles * 1 and LAPTM4B * 2. The risk of stomach cancer was increased 1.819 times in patients with genotype * 1 / 2 (CI=1.273-2.601) and 2.387 times in patients with genotype * 2 / 2 LAPTM4B (CI=1.195-4.767) compared with genotype * 1 / first. These studies indicate that allele * 2 LAPTM4B may be one of the genetic factors of gastric cancer. Further studies of newly described mutation moderately increased risk of stomach cancer may allow to estimate the real risk of gastric cancer associated with these mutations in the Polish population.

Overexpression of LAPTM4B promotes growth of gallbladder carcinoma cells in vitro

Background The overexpression of LAPTM4B-35 in gallbladder carcinoma (GBC) and its clinicopathologic and prognostic significance have been previously shown. Thus, this gene may play a role in the growth of GBC cells. Methods The pcDNA3-AE containing the complete open reading frame of LAPTM4B (lysosome-associated protein transmembrane-4β) and mock (pcDNA3) plasmids were transiently transfected into GBC-SD cells. Cell proliferation, cell cycle distribution, and protein expression were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium assay, flow cytometry, and Western blot, respectively. Results Cells transfected with pcDNA3-AE revealed accelerated proliferation, less serum dependence, and significant cell cycle progression compared with cells transfected with mock plasmid and parent cells. These phenotypes were accompanied by upregulated expression of C-myc, c-Fos, c-Jun, cyclin D1, and cyclin E and downregulated expression of P16 and P-27. Conclusions LAPTM4B overexpression promotes the growth of GBC cells in vitro by regulating the expression levels of some proliferation-associated proteins. Therefore, the LAPTM4B gene might be used as a novel therapeutic target of GBC.

Relationship between LAPTM4B gene polymorphism and susceptibility of colorectal and esophageal cancers

BackgroundLysosome-associated protein transmembrane 4 beta (LAPTM4B) is a novel gene of the mammalian LAPTM family and has been shown to be overexpressed in human hepatocellular carcinoma. There are two alleles, LAPTM4B*1 and *2, which share the same sequence except for one segment of 19 bp in the 5′ untranslated region of the exon 1. LAPTM4B*1 has one 19 bp segment, while LAPTM4B*2 has two tight tandem segments. The current case–control study was aimed to identify relationship between the gene polymorphism of LAPTM4B and the susceptibility of colorectal and esophageal cancers. Patients and methodsBlood samples were collected from patients with colon, rectal or esophageal cancers and control subjects. Genotypes of LAPTM4B were determined by PCR to detect differences between cancer cases (n=701) and healthy controls (n=350). Association between the LAPTM4B polymorphism and the risk of cancer was calculated by unconditional logistic regression models. ResultsWe found that there was a significant difference (P=0.0016) in allelic frequencies of LAPTM4B*2 between colon cancer cases (33.2%) and controls (24.1%). The risk of colon cancer was elevated significantly in cases with *1/2 genotype [odds ratio (OR)=1.474; 95% confidence interval (CI)=1.037–2.095] and *2/2 genotype (OR=2.531; 95% CI=1.316–4.868) when compared with the *1/1 genotype. No significant difference was observed for LAPTM4B*2 between the rectal or esophageal cancer cases when compared with the controls. The polymorphism in LAPTM4B was associated with increased risk of colon cancer but not of rectal and esophageal cancers. ConclusionsThese results indicate that the genetic polymorphism of LAPTM4B is a potential risk factor for the development of colon cancer.