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Abstract：
High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and hub-gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that PRKDC gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of PRKDC, has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of PRKDC in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. PRKDC and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC.
摘要：
高恶性是上皮性卵巢癌（EOC）的一个突出特征，强调进一步阐明癌症进展的潜在机制的必要性。非整倍体和拷贝数变异（CNV）部分导致EOC中观察到的恶性程度增加；然而，非整倍体的精确特征及其潜在的分子模式，以及EOC中CNV与非整倍体的关系，仍然不清楚。在这项研究中,我们利用单细胞测序数据和癌症基因组图谱(TCGA)研究EOC中的非整倍性和CNV.使用特异性探针采用荧光原位杂交（FISH）技术。评估染色体8的基因组区域内的拷贝数变异(42754568-47889815),并将其用作染色体8中单个细胞的倍性状态的代表性量度。基于染色体8倍性在不同亚组之间进行差异表达分析。基因本体论(GO)，京都基因和基因组百科全书（KEGG），蛋白质-蛋白质相互作用(PPI)，和hub基因分析随后被用来鉴定涉及的关键基因。通过根据8号染色体倍性结合TCGA数据整合将富集的肿瘤细胞分为不同的亚型，我们确定了EOC中驱动8号染色体非整倍体的关键基因，揭示PRKDC基因通过介导的非同源末端连接途径参与可能在疾病进展中起关键作用。通过分析GEO和TCGA数据库和生存评估进一步验证，考虑PRKDC的mRNA表达水平和CNV状态，已证实其参与了平等机会委员会的发展。进一步的功能分析显示PRKDC在卵巢EOC细胞和组织中上调,其表达与8号染色体上的拷贝数变异（CNV）的程度显着相关。一起来看,CNV扩增和8号染色体非整倍性是EOC的重要特征。PRKDC和介导的NHEJ途径可能在EOC进展期间驱动8号染色体上的非整倍体中起关键作用。
