Background: Osteoporosis (OP) is a common clinical manifestation of multiple myeloma (MM). The aim of this study was to investigate the possible molecular pathways and shared genes in the co-occurrence of OP and MM. M...Background: Osteoporosis (OP) is a common clinical manifestation of multiple myeloma (MM). The aim of this study was to investigate the possible molecular pathways and shared genes in the co-occurrence of OP and MM. Methods: The Gene Expression Omnibus database was used to retrieve gene expression information. Use WGCNA and differential analysis to screen out Hub genes. The GENEMANIA was used to build protein-protein interaction (PPI) networks. Enrichment analyses were performed to explore the functions. Validation datasets were selected to verify the diagnostic marker reliability of PLAGL1. The immune microenvironment of diseases was analyzed by immune infiltration analyses. Results: We confirmed a hub gene called PLAGL1, which is significantly under-expressed in both OP and MM. We found hub genes were associated with glucose and energy metabolism. Subsequently, the reliability of PLAGL1 for diagnosing OP and MM was verified using ROC curves, with all areas under the curve > 0.75. Moreover, PLAGL1 regulates t lymphocytes and may participate in the occurrence of OP in MM through immune pathways. Conclusions: PLAGL1 is a hub gene for the co-occurrence of OP and MM. It can regulate T-lymphocyte involvement in disease development. PLAGL1 may be a novel diagnostic marker for the co-occurrence of OP and MM.展开更多
AIM: To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics. METHODS: Methylation-specific PCR (MSP) assay was perfo...AIM: To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics. METHODS: Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic gastric adenocarcinoma, 30 intestinal-type gastric adenocarcinoma and 35 diffuse- type gastric adenocarcinoma samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher’s exact test to assess associations between methylation status and clinico- pathological characteristics. RESULTS: Hypermethylation frequencies of CDH1, FHIT, MTAP and PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hypermethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hypermethylation frequency wassignificantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender. CONCLUSION: Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.展开更多
文摘Background: Osteoporosis (OP) is a common clinical manifestation of multiple myeloma (MM). The aim of this study was to investigate the possible molecular pathways and shared genes in the co-occurrence of OP and MM. Methods: The Gene Expression Omnibus database was used to retrieve gene expression information. Use WGCNA and differential analysis to screen out Hub genes. The GENEMANIA was used to build protein-protein interaction (PPI) networks. Enrichment analyses were performed to explore the functions. Validation datasets were selected to verify the diagnostic marker reliability of PLAGL1. The immune microenvironment of diseases was analyzed by immune infiltration analyses. Results: We confirmed a hub gene called PLAGL1, which is significantly under-expressed in both OP and MM. We found hub genes were associated with glucose and energy metabolism. Subsequently, the reliability of PLAGL1 for diagnosing OP and MM was verified using ROC curves, with all areas under the curve > 0.75. Moreover, PLAGL1 regulates t lymphocytes and may participate in the occurrence of OP in MM through immune pathways. Conclusions: PLAGL1 is a hub gene for the co-occurrence of OP and MM. It can regulate T-lymphocyte involvement in disease development. PLAGL1 may be a novel diagnostic marker for the co-occurrence of OP and MM.
基金Supported by Fundao de Amparo à Pesquisa do Estado de So Paulo, Coordenao de Aperfeioamento de Pessoal de Nível Superior and Conselho Nacional de Desenvolvimento Científico e Tecnológico
文摘AIM: To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics. METHODS: Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic gastric adenocarcinoma, 30 intestinal-type gastric adenocarcinoma and 35 diffuse- type gastric adenocarcinoma samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher’s exact test to assess associations between methylation status and clinico- pathological characteristics. RESULTS: Hypermethylation frequencies of CDH1, FHIT, MTAP and PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hypermethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hypermethylation frequency wassignificantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender. CONCLUSION: Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.
