Table_4_Aberrant Gene Expression Profiling in Men With Sertoli Cell-Only Syndrome.docx

Sertoli cell-only syndrome (SCOS) is the most severe and common pathological type of non-obstructive azoospermia. The etiology of SCOS remains largely unknown to date despite a handful of studies reported in this area. According to the gene expression of testicular tissue samples in six datasets from the Gene Expression Omnibus, we detected 1441 differentially expressed genes (DEGs) between SCOS and obstructive azoospermia (OA) testicular tissue samples. Enriched GO terms and KEGG pathways for the downregulated genes included various terms and pathways related to cell cycle and reproduction, while the enrichment for the upregulated genes yielded many inflammation-related terms and pathways. In accordance with the protein-protein interaction (PPI) network, all genes in the most critical module belonged to the downregulated DEGs, and we obtained nine hub genes, including CCNB1, AURKA, CCNA2, BIRC5, TYMS, UBE2C, CDC20, TOP2A, and OIP5. Among these hub genes, six were also found in the most significant SCOS-specific module obtained from consensus module analysis. In addition, most of SCOS-specific modules did not have a consensus counterpart. Based on the downregulated genes, transcription factors (TFs) and kinases within the upstream regulatory network were predicted. Then, we compared the difference in infiltrating levels of immune cells between OA and SCOS samples and found a significantly higher degree of infiltration for most immune cells in SCOS than OA samples. Moreover, CD56bright natural killer cell was significantly associated with six hub genes. Enriched hallmark pathways in SCOS had remarkably more upregulated pathways than the downregulated ones. Collectively, we detected DEGs, significant modules, hub genes, upstream TFs and kinases, enriched downstream pathways, and infiltrated immune cells that might be specifically implicated in the pathogenesis of SCOS. These findings provide new insights into the pathogenesis of SCOS and fuel future advances in its theranostics.

索托利细胞唯一症候群（SCOS）系非阻塞性无精子症中最严重且最常见的病理类型。尽管该领域已有为数不多的研究报道，但SCOS的病因至今仍未被充分阐明。根据来自基因表达综合数据库的六个数据集中睾丸组织样本的基因表达情况，我们在SCOS与阻塞性无精子症（OA）睾丸组织样本之间检测到了1441个差异表达基因（DEGs）。下调基因的富集GO术语和KEGG通路包括与细胞周期和繁殖相关的多种术语和通路，而上调基因的富集则产生了许多与炎症相关的术语和通路。根据蛋白质-蛋白质相互作用（PPI）网络，最关键模块中的所有基因均属于下调的DEGs，并从中筛选出九个枢纽基因，包括CCNB1、AURKA、CCNA2、BIRC5、TYMS、UBE2C、CDC20、TOP2A和OIP5。在这九个枢纽基因中，有六个也出现在从共识模块分析中获得的最显著SCOS特异性模块中。此外，大多数SCOS特异性模块均未发现具有共识的对应物。基于下调基因，我们预测了上游调控网络中的转录因子（TFs）和激酶。随后，我们比较了OA和SCOS样本中免疫细胞的浸润水平，发现SCOS样本中大多数免疫细胞的浸润程度显著高于OA样本。此外，CD56bright自然杀伤细胞与六个枢纽基因显著相关。SCOS中富集的标志性通路具有比下调通路更为显著的上调通路。综合上述发现，我们检测到了DEGs、关键模块、枢纽基因、上游TFs和激酶、富集的下游通路以及浸润的免疫细胞，这些可能特定地涉及SCOS的发病机制。这些发现为SCOS的发病机制提供了新的见解，并为未来其在治疗诊断学方面的进展提供了动力。