Health Sciences Institute, China Medical University, Shenyang, 110122, Liaoning Province, China.
Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, China.
J Ovarian Res. 2024 Feb 12;17(1):38. doi: 10.1186/s13048-024-01361-z.
PCOS is a widespread disease that primarily caused in-pregnancy in pregnant-age women. Normoandrogen (NA) and Hyperandrogen (HA) PCOS are distinct subtypes of PCOS, while bio-markers and expression patterns for NA PCOS and HA PCOS have not been disclosed. We performed microarray analysis on granusola cells from NA PCOS, HA PCOS and normal tissue from 12 individuals. Afterwards, microarray data were processed and specific genes for NA PCOS and HA PCOS were identified. Further functional analysis selected IL6R and CD274 as new NA PCOS functional markers, and meanwhile selected CASR as new HA PCOS functional marker. IL6R, CD274 and CASR were afterwards experimentally validated on mRNA and protein level. Subsequent causal relationship analysis based on Apriori Rules Algorithm and co-occurrence methods identified classification markers for NA PCOS and HA PCOS. According to classification markers, downloaded transcriptome datasets were merged with our microarray data. Based on merged data, causal knowledge graph was constructed for NA PCOS or HA PCOS and female infertility on NA PCOS and HA PCOS. Gene-drug interaction analysis was then performed and drugs for HA PCOS and NA PCOS were predicted. Our work was among the first to indicate the NA PCOS and HA PCOS functional and classification markers and using markers to construct knowledge graphs and afterwards predict drugs for NA PCOS and HA PCOS based on transcriptome data. Thus, our study possessed biological and clinical value on further understanding the inner mechanism on the difference between NA PCOS and HA PCOS.
多囊卵巢综合征（PCOS）是一种广泛存在的疾病，主要发生在育龄期妇女的妊娠期间。正常雄激素（NA）和高雄激素（HA）PCOS 是 PCOS 的两种不同亚型，而 NA PCOS 和 HA PCOS 的生物标志物和表达模式尚未揭示。我们对 12 名个体的 NA PCOS、HA PCOS 和正常组织的颗粒细胞进行了微阵列分析。随后，对微阵列数据进行处理，确定了 NA PCOS 和 HA PCOS 的特定基因。进一步的功能分析选择了 IL6R 和 CD274 作为新的 NA PCOS 功能标志物，同时选择了 CASR 作为新的 HA PCOS 功能标志物。IL6R、CD274 和 CASR 随后在 mRNA 和蛋白质水平上进行了实验验证。基于 Apriori 规则算法和共现方法的后续因果关系分析确定了 NA PCOS 和 HA PCOS 的分类标志物。根据分类标志物，下载的转录组数据集与我们的微阵列数据合并。基于合并数据，为 NA PCOS 或 HA PCOS 和女性不孕症构建了关于 NA PCOS 和 HA PCOS 的因果知识图谱。随后进行了基因-药物相互作用分析，并预测了针对 HA PCOS 和 NA PCOS 的药物。我们的工作是首次指出 NA PCOS 和 HA PCOS 的功能和分类标志物，并使用标志物构建知识图谱，然后根据转录组数据预测针对 NA PCOS 和 HA PCOS 的药物。因此，我们的研究对进一步了解 NA PCOS 和 HA PCOS 之间差异的内在机制具有生物学和临床价值。
