基于生物信息学数据库分析CDCA8 mRNA在卵巢癌中的表达及其临床意义

Analysis of expression level of CDCA8 mRNA in ovarian cancer based on bioinformatics database and its clinical significance

目的基于生物信息学数据库分析细胞分裂周期相关蛋白8(Cell division cycle associated 8,CDCA8)mRNA在卵巢癌中的表达水平及其生物学功能。方法GEPIA数据库中下载卵巢癌转录组数据集,分析CDCA8 mRNA在卵巢癌组织和正常卵巢组织中的表达差异。K-M数据库分析卵巢癌CDCA8 mRNA高表达组和低表达组生存率的差异。ULACAN数据库筛选卵巢癌中与CDCA8的共表达基因并进行GO和KEGG富集分析,TIMER数据库中通过Spearman法分析卵巢癌中CDCA8 mRNA的表达水平与多种免疫细胞浸润程度的关系。选择2022年1-8月本院收治的75例卵巢癌患者作为研究对象,设为卵巢癌组;另选同期75名健康体检者作为对照组。免疫组化法分析CDCA8在卵巢癌组织和癌旁组织中的表达差异,卵巢癌组和对照组血清中CDCA8表达水平的差异采用ELISA法分析。结果卵巢癌组织和正常卵巢组织中CDCA8 mRNA表达水平分别为3.89(3.23,4.42)和0.84(0.53,0.91),卵巢癌组织中CDCA8 mRNA表达水平显著升高,差异具有统计学意义(P<0.05)。卵巢癌CDCA8 mRNA高表达组和低表达组中位生存时间分别为18.23个月和20.56个月,卵巢癌CDCA8 mRNA高表达组生存率显著降低(HR=1.18,P=0.011)。卵巢癌中与CDCA8具有显著正相关性的共表达基因427个,共表达基因富集的CC包括核浆、核、细胞质、着丝粒和纺锤体,MF包括蛋白结合、ATP结合、微管结合、染色质结合和ATP酶活性,BP包括细胞分裂、G2/M有丝分裂细胞周期转变、DNA复制、有丝分裂纺锤体组织和染色体隔离,KEGG包括细胞周期、DNA复制、卵母细胞减数分裂、孕激素介导的卵母细胞成熟和p53信号通路。卵巢癌中CDCA8 mRNA与B细胞(r=0.108,P=0.001)、CD4+T淋巴细胞(r=0.107,P=0.001)及巨噬细胞(r=0.117,P=0.001)浸润程度具有显著正相关性。免疫组化结果显示,卵巢癌组织中CDCA8高度表达50例,中度12表达、低度表达13例,高表达率为82.67%,75例卵巢癌旁组织中CDCA8均为低度表达,CDCA8高表达率在卵巢癌组织中显著高于癌旁组织,差异具有统计学意义(χ^(2)=105.68,P<0.001)。卵巢患者和对照组血清中CDCA8的表达水平分别为(87.23±6.45)mg/ml、(34.91±5.88)mg/ml,与对照组比较,血清中CDCA8在卵巢癌组中显著升高,差异具有统计学意义(t=51.91,P<0.001)。结论CDCA8在卵巢癌中显著高表达,可能是通过调控细胞周期及免疫细胞浸润等方式参与卵巢癌的进展,CDCA8可作为卵巢癌患者预后不良的一项生物学标志物。

Objective To analyze the expression level of CDCA8 mRNA in ovarian cancer based on bioinformatics database and its biological function.Methods The ovarian cancer transcriptome dataset was downloaded from the GEPIA database,and the expression difference of CDCA8 mRNA in ovarian cancer and normal ovarian tissue was analyzed.The survival rate difference between the high and low expression groups of CDCA8 mRNA was analyzed using the K-M database.The genes co-expressed with CDCA8 in ovarian cancer were screened in the ULACAN database,and all co-expressed genes were further analyzed for GO and KEGG enrichment.The relationship between the expression level of CDCA8 mRNA and the degree of infiltration of multiple immune cells in ovarian cancer was analyzed using the Spearman method in the TIMER database.A total of 75 patients with ovarian cancer(ovarian cancer group)and 75 healthy controls(control group)were enrolled in Nanyang Central Hospital between January 2022 and August 2022.The expression level of CDCA8 in ovarian cancer tissues and adjacent tissues was analyzed by immunohistochemistry,and the expression level of CDCA8 in serum between the ovarian cancer group and the control group was analyzed by ELISA methods.Results The expression levels of CDCA8 mRNA in ovarian cancer and normal ovarian tissues were 3.89(3.23,4.42)and 0.84(0.53,0.91),respectively.The expression levels of CDCA8 mRNA in ovarian cancer tissues were significantly increased,and the difference was statistically significant(P<0.05).The median survival time of CDCA8 mRNA high expression group and the low expression group was 18.23 months and 20.56 months,respectively.The survival rate of the CDCA8 mRNA high expression group was significantly reduced(HR=1.18,P=0.011).There were 427 co-expressed genes exist significant positive correlation with CDCA8 in ovarian cancer.The co-expressed gene enriched CC including cytoplasm,nucleus,cytoplasm,centromere and spindle,while MF including protein binding,ATP binding,microtubule binding,chromatin binding and ATPase activity.The BP including cell division,G2/M mitotic cell cycle transition,DNA replication,mitotic spindle organization,and chromosome isolation,while KEGG including cell cycle,DNA replication,oocyte meiosis,progesterone mediated oocyte maturation,and p53 signaling pathways.There was a significant positive correlation between CDCA8 mRNA and the infiltration degree of B cells(r=0.108,P=0.001),CD4+T lymphocytes(r=0.107,P=0.001)and macrophages(r=0.117,P=0.001)in ovarian cancer.The immunohistochemical results showed that there were 50 cases of CDCA8 mRNA high expression in ovarian cancer tissues,12 cases with moderate expression,and 13 cases with low expression,the high expression rate was 82.67%.The 75 cases of adjacent tissues of ovarian cancer were showed with low expression of CDCA8,and the high expression rate of CDCA8 in ovarian cancer tissues was significantly higher than that in adjacent tissues.The difference was statistically significant(χ^(2)=105.68,P<0.001).The expression level of serum CDCA8 in ovarian patients and control group was(87.23±6.45)mg/ml and(34.91±5.88)mg/ml,respectively.Compared with the control group,the serum CDCA8 level in ovarian cancer group was significantly increased,and the difference was statistically significant(t=51.91,P<0.001).Conclusions CDCA8 is highly expressed in ovarian cancer,which may be involved in the progression of ovarian cancer through the regulation of the cell cycle and immune cell infiltration.CDCA8 can be used as a biological marker for poor prognosis in ovarian cancer patients.