Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer.This study aimed to evaluate the prognostic significance of the 21-gene recurrence score(RS)in Chinese patients with...Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer.This study aimed to evaluate the prognostic significance of the 21-gene recurrence score(RS)in Chinese patients with pN0-l,estrogen receptor-positive(ER+),human epidermal growth factor receptor 2-negative(HER2)breast cancer.Among 800 patients recruited between 2009 and 2016,the median RS was 24(0-69),with 27.4%,46.8%,and 25.9%patients classified into low-,intermediate-,and high-risk groups.Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival(IDFS)and distant disease-free survival(DDFS)events compared with the low-risk category(IDFS:HR=2.450,95%Cl 1.017-5.902,P=0.046;DDFS:HR=2.829,95%Cl 1.013-7.901,P=0.047).No significant association between RS category and overall survival(OS)was found(intermediate vs.low:HR=1.244,95%Cl 0.292-5.297,P=0.768;high vs.low:HR=2.933,95%Cl 0.759-11.327,P=0.119).RS,as a continuous variable,was a highly significant predictor for IDFS(HR=1.028,95%Cl 1.010-1.047,P=0.002),DDFS(HR=1.030,95%Cl 1.010-1.051,P=0.003),and OS(HR=1.034,95%Cl 1.007-1.063,P=0.014).Our findings suggested that RS may predict IDFS in Chinese patients with ER+/HER2 breast cancer with NO or N1 disease.展开更多
【目的】试验旨在对hsa-miR-21-5p的序列保守性和靶基因进行生物信息学分析,为进一步探讨其在卵母细胞成熟过程中的功能及调节机制提供思路。【方法】从GEO数据库获取人卵母细胞不同成熟阶段对应的卵丘细胞基因表达谱数据(GSE31681),利...【目的】试验旨在对hsa-miR-21-5p的序列保守性和靶基因进行生物信息学分析,为进一步探讨其在卵母细胞成熟过程中的功能及调节机制提供思路。【方法】从GEO数据库获取人卵母细胞不同成熟阶段对应的卵丘细胞基因表达谱数据(GSE31681),利用R软件筛选差异表达基因(DEGs),通过FunRich软件预测DEGs的靶向miRNAs,找出hsa-miR-21-5p靶向的DEGs,获得miRNA-mRNA关系对;利用BLAST程序进行相似性比对,通过Mega 11.0软件构建系统进化树,采用ViennaRNA Web Services预测pre-miR-21-5p的二级结构;使用miRTarBase网站预测hsa-miR-21-5p靶基因,并进行GO功能和KEGG通路富集分析;通过STRING数据库建立蛋白质互作网络,并利用Cytoscape软件进行可视化分析。【结果】共筛选出7个卵母细胞成熟过程中GV/MⅡ期对应卵丘细胞中hsa-miR-21-5p靶向的DEGs。对物种间miR-21-5p序列分析发现,人pre-miR-21-5p与小鼠、褐家鼠、黄牛、绵羊、笔尾树鼩、猕猴的相似性均达95%以上,且miR-21-5p在进化过程中高度保守。ViennaRNA Web Services预测结果显示,pre-miR-21-5p的二级结构具有典型的单一茎环结构。靶基因预测发现,hsa-miR-21-5p共有潜在的723个靶基因。GO功能富集结果显示,靶基因主要富集到细胞增殖调控、内源性凋亡信号通路、蛋白激酶活性的正向调节等功能。KEGG通路富集表明,靶基因主要富集到MAPK和p53等信号通路。蛋白互作分析发现,靶基因MYC、FOXO 3、STAT 3等编码的蛋白与其他蛋白存在较多靶向关系,参与了PI3K/Akt、JAK-STAT等信号通路。【结论】miR-21-5p在生物进化过程中具有高度保守性,其主要通过调节卵丘细胞中相关基因的表达来调控MAPK和p53等信号通路,进而在卵母细胞成熟过程中发挥作用。展开更多
基金This work was supported by grants from the Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission(Nos.14411-950200 and 14411950201)the National Natural Science Foundation of China(No.81772797)the Shanghai Municipal Commission of Health and Family Planning(No.201840323)。
文摘Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer.This study aimed to evaluate the prognostic significance of the 21-gene recurrence score(RS)in Chinese patients with pN0-l,estrogen receptor-positive(ER+),human epidermal growth factor receptor 2-negative(HER2)breast cancer.Among 800 patients recruited between 2009 and 2016,the median RS was 24(0-69),with 27.4%,46.8%,and 25.9%patients classified into low-,intermediate-,and high-risk groups.Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival(IDFS)and distant disease-free survival(DDFS)events compared with the low-risk category(IDFS:HR=2.450,95%Cl 1.017-5.902,P=0.046;DDFS:HR=2.829,95%Cl 1.013-7.901,P=0.047).No significant association between RS category and overall survival(OS)was found(intermediate vs.low:HR=1.244,95%Cl 0.292-5.297,P=0.768;high vs.low:HR=2.933,95%Cl 0.759-11.327,P=0.119).RS,as a continuous variable,was a highly significant predictor for IDFS(HR=1.028,95%Cl 1.010-1.047,P=0.002),DDFS(HR=1.030,95%Cl 1.010-1.051,P=0.003),and OS(HR=1.034,95%Cl 1.007-1.063,P=0.014).Our findings suggested that RS may predict IDFS in Chinese patients with ER+/HER2 breast cancer with NO or N1 disease.
文摘【目的】试验旨在对hsa-miR-21-5p的序列保守性和靶基因进行生物信息学分析,为进一步探讨其在卵母细胞成熟过程中的功能及调节机制提供思路。【方法】从GEO数据库获取人卵母细胞不同成熟阶段对应的卵丘细胞基因表达谱数据(GSE31681),利用R软件筛选差异表达基因(DEGs),通过FunRich软件预测DEGs的靶向miRNAs,找出hsa-miR-21-5p靶向的DEGs,获得miRNA-mRNA关系对;利用BLAST程序进行相似性比对,通过Mega 11.0软件构建系统进化树,采用ViennaRNA Web Services预测pre-miR-21-5p的二级结构;使用miRTarBase网站预测hsa-miR-21-5p靶基因,并进行GO功能和KEGG通路富集分析;通过STRING数据库建立蛋白质互作网络,并利用Cytoscape软件进行可视化分析。【结果】共筛选出7个卵母细胞成熟过程中GV/MⅡ期对应卵丘细胞中hsa-miR-21-5p靶向的DEGs。对物种间miR-21-5p序列分析发现,人pre-miR-21-5p与小鼠、褐家鼠、黄牛、绵羊、笔尾树鼩、猕猴的相似性均达95%以上,且miR-21-5p在进化过程中高度保守。ViennaRNA Web Services预测结果显示,pre-miR-21-5p的二级结构具有典型的单一茎环结构。靶基因预测发现,hsa-miR-21-5p共有潜在的723个靶基因。GO功能富集结果显示,靶基因主要富集到细胞增殖调控、内源性凋亡信号通路、蛋白激酶活性的正向调节等功能。KEGG通路富集表明,靶基因主要富集到MAPK和p53等信号通路。蛋白互作分析发现,靶基因MYC、FOXO 3、STAT 3等编码的蛋白与其他蛋白存在较多靶向关系,参与了PI3K/Akt、JAK-STAT等信号通路。【结论】miR-21-5p在生物进化过程中具有高度保守性,其主要通过调节卵丘细胞中相关基因的表达来调控MAPK和p53等信号通路,进而在卵母细胞成熟过程中发挥作用。
