BACKGROUND Colorectal cancer(CRC)is one of the most malignant gastrointestinal cancers worldwide.The liver is the most important metastatic target organ,and liver metastasis is the leading cause of death in patients w...BACKGROUND Colorectal cancer(CRC)is one of the most malignant gastrointestinal cancers worldwide.The liver is the most important metastatic target organ,and liver metastasis is the leading cause of death in patients with CRC.Owing to the lack of sensitive biomarkers and unclear molecular mechanism,the occurrence of liver metastases cannot be predicted and the clinical outcomes are bad for liver metastases.Therefore,it is very important to identify the diagnostic or prognostic markers for liver metastases of CRC.AIM To investigate the highly differentially expressed genes(HDEGs)and prognostic marker for liver metastases of CRC.METHODS Data from three NCBI Gene Expression Omnibus(GEO)datasets were used to show HDEGs between liver metastases of CRC and tumour or normal samples.These significantly HDEGs of the three GEO datasets take the interactions.And these genes were screened through an online tool to explore the prognostic value.Then,TIMER and R package were utilized to investigate the immunity functions of the HDEGs and gene set enrichment analysis was used to explore their potential functions.RESULTS Based on the selection criteria,three CRC datasets for exploration(GSE14297,GSE41258,and GSE49355)were chosen.Venn diagrams were used to show HDEGs common to the six groups and 47 HDEGs were obtained.The HDEGs were shown by using STRING and Cytoscape software.Based on the TCGA database,APOC1 showed significantly different expression between N2 and N0,and N2 and N1.And there was also a significant difference in expression between T2 and T4,and between T2 and T3.In 20 paired CRC and normal tissues,quantitative real-time polymerase chain reaction illustrated that the APOC1 mRNA was strongly upregulated in CRC tissues(P=0.014).PrognoScan and GEPIA2 revealed the prognostic value of APOC1 for overall survival and diseasefree survival in CRC(P<0.05).TIMER showed that APOC1 has a close relationship with immune infiltration(P<0.05).CONCLUSION APOC1 is a biomarker that is associated with both the diagnosis and prognosis of liver metastases of CRC.展开更多
Breast cancer is one of the most common malignant tumors with high mortality and poor prognosis in women.There is an urgent need to discover new therapeutic targets for breast cancer metastasis.Herein,we identified th...Breast cancer is one of the most common malignant tumors with high mortality and poor prognosis in women.There is an urgent need to discover new therapeutic targets for breast cancer metastasis.Herein,we identified that Apolipoprotein C1(APOC1)was up-regulated in primary tumor of breast cancer patient that recurrence and metastasis by immunohistochemistry(IHC).Kaplan-Meier Plotter database showed that high levels of APOC1 in breast cancer patients were strongly associated with worse overall survival(OS)and relapse-free survival(RFS).Mechanistically,APOC1 silencing significantly inhibits MAPK/ERK kinase pathway and restrains the NF-κB to decrease the transcription of target genes related to growth and metastasis in vitro.Based on this regulatory mechanism,we developed these findings into potential therapeutic drugs,glutathione(GSH)responsive nanoparticles(NPs)were used for systemic APOC1 siRNA delivery,NPs(siAPOC1)silenced APOC1 expression,and subsequently resulted in positive anti-tumor effects in orthotopic and liver metastasis models in vivo.Taken together,GSH responsive NPmediated siAPOC1 delivery was proved to be effective in regulating growth and metastasis in multiple tumor models.These findings show that APOC1 could be a potential biomarker to predict the prognosis of breast cancer patients and NP-mediated APOC1 silencing could be new strategies for exploration of new treatments for breast cancer metastasis.展开更多
基金National Key Research and Development(R&D)Program Project,No.2019YFC1315705.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most malignant gastrointestinal cancers worldwide.The liver is the most important metastatic target organ,and liver metastasis is the leading cause of death in patients with CRC.Owing to the lack of sensitive biomarkers and unclear molecular mechanism,the occurrence of liver metastases cannot be predicted and the clinical outcomes are bad for liver metastases.Therefore,it is very important to identify the diagnostic or prognostic markers for liver metastases of CRC.AIM To investigate the highly differentially expressed genes(HDEGs)and prognostic marker for liver metastases of CRC.METHODS Data from three NCBI Gene Expression Omnibus(GEO)datasets were used to show HDEGs between liver metastases of CRC and tumour or normal samples.These significantly HDEGs of the three GEO datasets take the interactions.And these genes were screened through an online tool to explore the prognostic value.Then,TIMER and R package were utilized to investigate the immunity functions of the HDEGs and gene set enrichment analysis was used to explore their potential functions.RESULTS Based on the selection criteria,three CRC datasets for exploration(GSE14297,GSE41258,and GSE49355)were chosen.Venn diagrams were used to show HDEGs common to the six groups and 47 HDEGs were obtained.The HDEGs were shown by using STRING and Cytoscape software.Based on the TCGA database,APOC1 showed significantly different expression between N2 and N0,and N2 and N1.And there was also a significant difference in expression between T2 and T4,and between T2 and T3.In 20 paired CRC and normal tissues,quantitative real-time polymerase chain reaction illustrated that the APOC1 mRNA was strongly upregulated in CRC tissues(P=0.014).PrognoScan and GEPIA2 revealed the prognostic value of APOC1 for overall survival and diseasefree survival in CRC(P<0.05).TIMER showed that APOC1 has a close relationship with immune infiltration(P<0.05).CONCLUSION APOC1 is a biomarker that is associated with both the diagnosis and prognosis of liver metastases of CRC.
基金supported by the National Natural Science Foundation of China(81570764)Guangzhou Science and Technology Project(201807010069)+2 种基金Shenzhen Science and Technology Project(JCYJ20190807154205627)Guangdong Natural Science Fund(2020A1515010365)Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population(2018B030322003KF01).
文摘Breast cancer is one of the most common malignant tumors with high mortality and poor prognosis in women.There is an urgent need to discover new therapeutic targets for breast cancer metastasis.Herein,we identified that Apolipoprotein C1(APOC1)was up-regulated in primary tumor of breast cancer patient that recurrence and metastasis by immunohistochemistry(IHC).Kaplan-Meier Plotter database showed that high levels of APOC1 in breast cancer patients were strongly associated with worse overall survival(OS)and relapse-free survival(RFS).Mechanistically,APOC1 silencing significantly inhibits MAPK/ERK kinase pathway and restrains the NF-κB to decrease the transcription of target genes related to growth and metastasis in vitro.Based on this regulatory mechanism,we developed these findings into potential therapeutic drugs,glutathione(GSH)responsive nanoparticles(NPs)were used for systemic APOC1 siRNA delivery,NPs(siAPOC1)silenced APOC1 expression,and subsequently resulted in positive anti-tumor effects in orthotopic and liver metastasis models in vivo.Taken together,GSH responsive NPmediated siAPOC1 delivery was proved to be effective in regulating growth and metastasis in multiple tumor models.These findings show that APOC1 could be a potential biomarker to predict the prognosis of breast cancer patients and NP-mediated APOC1 silencing could be new strategies for exploration of new treatments for breast cancer metastasis.
文摘目的:探讨载脂蛋白C1(apolipoprotein C1,APOC1)基因多态性与缺血性中风易感性及临床指标的相关性。方法:选择广西中医药大学第一附属医院脑病二科533例缺血性脑卒中患者为病例组,并选择同时期该院体检中心健康体检者或骨科及其他病势较轻的外伤患者531例为对照组。应用Sequenom技术对APOC1基因rs4420638位点进行基因分型。应用PLINK软件进行遗传关联分析。结果:两组受试者rs4420683的基因型频率比较,差异具有统计学意义(χ^(2)=8.725 P=0.013);在显性模型、隐形模型、加性模型中,APOC1基因rs4420683多态性与缺血性中风痰瘀证发生风险的关联比较,差异无统计学意义(P>0.05);经年龄、性别校正后,关联仍无统计学意义(P_(adj)>0.05);按性别分层分析,在男性、女性受试者中,APOC1基因的多态性与缺血性中风痰瘀证发生风险的关联均无统计学意义(P>0.05);校正年龄后,关联仍无统计学意义(P_(adj)>0.05)。在校正性别、年龄后结果显示,APOC1基因多态性与缺血性中风痰瘀证患者收缩压、舒张压水平的相关性比较,差异均无统计学意义(P_(adj)>0.05);APOC1基因rs4420683多态性与缺血性中风痰瘀证患者空腹血糖及餐后2 h血糖的相关性比较,差异均无统计学意义(P_(adj)>0.05);APOC1基因多态性与缺血性中风痰瘀证患者的高密度脂蛋白(high density lipoprotein,HDL)[显性模型:β=0.09,95%CI(0.02,0.16),P=0.010)]、低密度脂蛋白(low density lipoprotein,LDL)[显性模型:β=0.25,95%CI(0.03,0.46),P=0.025)]显著相关;rs4420683多态性与缺血性中风痰瘀证患者HDL[显性模型:β_(adj)=0.08,95%CI adj(0.01,0.15),P_(adj)=0.021]、LDL[显性模型:β_(adj)=0.23,95%CI adj(0.01,0.44),P_(adj)=0.037]也具有相关性。结论:APOC1基因rs4420638的多态性可能会对缺血性中风痰瘀证的发生和发展产生影响,其作用机制可能涉及对血脂代谢的调节。
