Kaposi肉瘤（KS）是由Kaposi肉瘤疱疹病毒（KSHV）引起的多中心肿瘤，在全球范围内导致HIV感染者的患病率和死亡率上升。KS通常涉及皮肤，但在严重病例中也可能发生在胃肠道（GI）。我们使用RNA测序来比较来自19个参与者的44对样本的皮肤和GI KS病变的细胞和KSHV基因表达特征。对KS病变的KSHV表达分析确定了病毒基因组的转录活跃区域。一个重要的病毒裂解基因ORF75的转录物在91％的KS病变中被检测到。宿主基因分析鉴定了在皮肤KS和GI KS病变中与正常组织相比独特的370个差异表达基因（DEGs）和58个差异表达基因。与正常皮肤相比，白细胞介素（IL）-6和IL-10基因表达在皮肤病变中较高，但在GI KS病变中并未发现。在皮肤和GI KS组织中，有26个细胞基因差异表达：包括编码血管生成受体的Fms相关酪氨酸激酶4（FLT4）和分泌性糖蛋白的Stanniocalcin 1（STC1）。使用原代淋巴管内皮细胞（LECs）进行的功能研究进一步调查了FLT4和STC1。在这些模型中，LECs的KSHV感染导致了管状形成的增加，而STC1或FLT4的沉默则导致了管状形成的受损。此项KS组织的转录谱研究为这种独特的病毒驱动肿瘤的特征和发病机制提供了新见解。© 2023. BioMed Central Ltd., Springer Nature的一部分。

Kaposi sarcoma (KS) is a multicentric tumor caused by Kaposi sarcoma herpesvirus (KSHV) that leads to morbidity and mortality among people with HIV worldwide. KS commonly involves the skin but can occur in the gastrointestinal tract (GI) in severe cases.RNA sequencing was used to compare the cellular and KSHV gene expression signatures of skin and GI KS lesions in 44 paired samples from 19 participants with KS alone or with concurrent KSHV-associated diseases. Analyses of KSHV expression from KS lesions identified transcriptionally active areas of the viral genome.The transcript of an essential viral lytic gene, ORF75, was detected in 91% of KS lesions. Analyses of host genes identified 370 differentially expressed genes (DEGs) unique to skin KS and 58 DEGs unique to GI KS lesions as compared to normal tissue. Interleukin (IL)-6 and IL-10 gene expression were higher in skin lesions as compared to normal skin but not in GI KS lesions. Twenty-six cellular genes were differentially expressed in both skin and GI KS tissues: these included Fms-related tyrosine kinase 4 (FLT4), encoding an angiogenic receptor, and Stanniocalcin 1 (STC1), a secreted glycoprotein. FLT4 and STC1 were further investigated in functional studies using primary lymphatic endothelial cells (LECs). In these models, KSHV infection of LECs led to increased tubule formation that was impaired upon knock-down of STC1 or FLT4.This study of transcriptional profiling of KS tissue provides novel insights into the characteristics and pathogenesis of this unique virus-driven neoplasm.© 2023. BioMed Central Ltd., part of Springer Nature.