Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. P...Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori(H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Downregulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advancedstage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.展开更多
Objective:Modern medical research has proven that human diseases are directly or indirectly related to genes.At the same time,genetic research has also brought updates to diagnostic techniques.Olfactomedin-like 3 (OLF...Objective:Modern medical research has proven that human diseases are directly or indirectly related to genes.At the same time,genetic research has also brought updates to diagnostic techniques.Olfactomedin-like 3 (OLFML3) gene is a novel and clinically valuable gene.In order to better understand the role of OLFML3 in human diseases,we discuss and analyze the characteristics,function,and regulation mechanism of the OLFML3 gene in this review.Data sources:A comprehensive search in PubMed and ScienceDirect database for English up to March 2019,with the keywords of "Olfactomedin-like 3,""Olfactomedin,""extracellular matrix,""Transforming Growth Factor β1,""anoikis-resistance," and "microRNA-155." Study selection:Careful review of all relevant literature,the references of the retrieved articles were also screened to search for potentially relevant papers.Results:OLFML3 is a secreted glycoprotein with 406 amino acid residues,belonging to the Olfactomedin (OLF) family.Due to the particularity of its structure and differential expression,OLFML3 has unique biological functions that could be distinct from other members in the OLF family.The currently known functions include embryonic development function and tumorigenesis.The regulation mechanism is still under investigation.It is directly related to many human diseases.Conclusions:OLFML3 is a mukifunctional glycoprotein that is closely involved in embryonic development,tumor invasion,and metastasis.Unfortunately,current research on this important molecule is still very limited.Further investigations on the possible mechanism of OLFML3 biological functions and modulation will help us develop better diagnostics and treatments.展开更多
目的以生物信息学方法分析嗅质蛋白样蛋白2B(OLFML2B)基因在肝细胞癌中的表达情况及其临床意义。方法通过分析生物医学数据分析盒子(Sangerbox)数据库、癌症基因组图谱(TCGA)数据库获得OLFML2B基因在肝细胞癌组织及正常肝组织中的表达...目的以生物信息学方法分析嗅质蛋白样蛋白2B(OLFML2B)基因在肝细胞癌中的表达情况及其临床意义。方法通过分析生物医学数据分析盒子(Sangerbox)数据库、癌症基因组图谱(TCGA)数据库获得OLFML2B基因在肝细胞癌组织及正常肝组织中的表达情况和生存情况。分析肿瘤免疫评估资源(TIMER)数据库获得OLFML2B基因与肝细胞癌组织免疫浸润水平的相关性。分析伯明翰阿拉巴马大学癌症数据分析门户网站(UALCAN)数据库、cBio癌症基因组学门户网站(cBioProtal)数据库获得OLFML2B基因启动子区甲基化水平及突变情况。分析TCGA多组学关联分析(LinkedOmics)数据库获得OLFML2B基因导致肝细胞癌发生所涉及的生物学过程和信号通路。结果Sangerbox数据库分析结果显示,OLFML2B基因在多数肿瘤组织的mRNA表达水平高于正常组织,在肝细胞癌中表达量高于正常组织(P<0.001)。TCGA数据库分析结果显示,在配对及非配对的肝细胞癌组织与正常组织中,OLFML2B基因的表达水平显著均高于正常组织(P<0.001)。单因素分析结果表明,OLFML2B基因表达量与年龄、性别、体质量指数(BMI)、病理分期、甲胎蛋白(AFP)、血管浸润等均无相关性(P>0.05)。Kaplan-Meier生存分析结果表明,OLFML2B基因低表达的肝细胞癌患者的总生存率、疾病特异性生存率均高于OLFML2B基因高表达的肝细胞癌患者(P<0.05)。TIMER数据库分析结果显示,肝细胞癌中OLFML2B基因表达与B细胞、CD8^(+)T细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞、树突状细胞等细胞免疫浸润呈正相关(P<0.05)。UALCAN数据库分析结果显示,OLFML2B基因启动子区甲基化水平高于正常组织(P<0.05)。cBioProtal数据库分析结果显示,OLFML2B基因在肝细胞癌中已被收录4个突变,均为错义突变,突变后蛋白发生改变。LinkedOmics数据库基因富集分析结果发现,OLFML2B基因与免疫系统的正向调节、血管生成、细胞迁移的正向调节、细胞运动的正向调节、胞外分泌调节、免疫应答、细胞凋亡等生物学过程有关。京都基因与基因组百科全书(KEGG)富集分析结果显示,OLFML2B基因与Ras、MAPK、PI3K、pathway in cancer等信号通路有关。结论OLFML2B基因在肝细胞癌组织中高表达。OLFML2B基因低表达的肝细胞癌患者的预后较好。OLFML2B基因与免疫浸润有关。肝细胞癌发生的机制可能与OLFML2B基因启动子区甲基化、错义突变、血管生成、细胞迁移的正向调节、Ras、MAPK、PI3K、pathway in cancer等信号通路有关。展开更多
基金Supported by the National Natural Science Foundation of China,No.81470838the Science Foundation of Health Bureau of Zhejiang Province,No.2015KYB030
文摘Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori(H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Downregulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advancedstage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.
文摘Objective:Modern medical research has proven that human diseases are directly or indirectly related to genes.At the same time,genetic research has also brought updates to diagnostic techniques.Olfactomedin-like 3 (OLFML3) gene is a novel and clinically valuable gene.In order to better understand the role of OLFML3 in human diseases,we discuss and analyze the characteristics,function,and regulation mechanism of the OLFML3 gene in this review.Data sources:A comprehensive search in PubMed and ScienceDirect database for English up to March 2019,with the keywords of "Olfactomedin-like 3,""Olfactomedin,""extracellular matrix,""Transforming Growth Factor β1,""anoikis-resistance," and "microRNA-155." Study selection:Careful review of all relevant literature,the references of the retrieved articles were also screened to search for potentially relevant papers.Results:OLFML3 is a secreted glycoprotein with 406 amino acid residues,belonging to the Olfactomedin (OLF) family.Due to the particularity of its structure and differential expression,OLFML3 has unique biological functions that could be distinct from other members in the OLF family.The currently known functions include embryonic development function and tumorigenesis.The regulation mechanism is still under investigation.It is directly related to many human diseases.Conclusions:OLFML3 is a mukifunctional glycoprotein that is closely involved in embryonic development,tumor invasion,and metastasis.Unfortunately,current research on this important molecule is still very limited.Further investigations on the possible mechanism of OLFML3 biological functions and modulation will help us develop better diagnostics and treatments.
文摘目的以生物信息学方法分析嗅质蛋白样蛋白2B(OLFML2B)基因在肝细胞癌中的表达情况及其临床意义。方法通过分析生物医学数据分析盒子(Sangerbox)数据库、癌症基因组图谱(TCGA)数据库获得OLFML2B基因在肝细胞癌组织及正常肝组织中的表达情况和生存情况。分析肿瘤免疫评估资源(TIMER)数据库获得OLFML2B基因与肝细胞癌组织免疫浸润水平的相关性。分析伯明翰阿拉巴马大学癌症数据分析门户网站(UALCAN)数据库、cBio癌症基因组学门户网站(cBioProtal)数据库获得OLFML2B基因启动子区甲基化水平及突变情况。分析TCGA多组学关联分析(LinkedOmics)数据库获得OLFML2B基因导致肝细胞癌发生所涉及的生物学过程和信号通路。结果Sangerbox数据库分析结果显示,OLFML2B基因在多数肿瘤组织的mRNA表达水平高于正常组织,在肝细胞癌中表达量高于正常组织(P<0.001)。TCGA数据库分析结果显示,在配对及非配对的肝细胞癌组织与正常组织中,OLFML2B基因的表达水平显著均高于正常组织(P<0.001)。单因素分析结果表明,OLFML2B基因表达量与年龄、性别、体质量指数(BMI)、病理分期、甲胎蛋白(AFP)、血管浸润等均无相关性(P>0.05)。Kaplan-Meier生存分析结果表明,OLFML2B基因低表达的肝细胞癌患者的总生存率、疾病特异性生存率均高于OLFML2B基因高表达的肝细胞癌患者(P<0.05)。TIMER数据库分析结果显示,肝细胞癌中OLFML2B基因表达与B细胞、CD8^(+)T细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞、树突状细胞等细胞免疫浸润呈正相关(P<0.05)。UALCAN数据库分析结果显示,OLFML2B基因启动子区甲基化水平高于正常组织(P<0.05)。cBioProtal数据库分析结果显示,OLFML2B基因在肝细胞癌中已被收录4个突变,均为错义突变,突变后蛋白发生改变。LinkedOmics数据库基因富集分析结果发现,OLFML2B基因与免疫系统的正向调节、血管生成、细胞迁移的正向调节、细胞运动的正向调节、胞外分泌调节、免疫应答、细胞凋亡等生物学过程有关。京都基因与基因组百科全书(KEGG)富集分析结果显示,OLFML2B基因与Ras、MAPK、PI3K、pathway in cancer等信号通路有关。结论OLFML2B基因在肝细胞癌组织中高表达。OLFML2B基因低表达的肝细胞癌患者的预后较好。OLFML2B基因与免疫浸润有关。肝细胞癌发生的机制可能与OLFML2B基因启动子区甲基化、错义突变、血管生成、细胞迁移的正向调节、Ras、MAPK、PI3K、pathway in cancer等信号通路有关。
