透镜上皮源性生长因子（LEDGF/p75）是表观遗传标记的识别者，也是治疗干预的潜在靶点。其在人类免疫缺陷病毒（HIV）整合和由MLL（又称KMT2A）基因融合驱动的白血病发展中的参与使其成为药物开发的理想候选。然而，关于LEDGF/p75作为肿瘤中H3K36me3表观遗传读取者的探索还有限。在此，我们首次通过多个在线数据库和体外实验分析了LEDGF/p75在多种癌症中的作用。我们使用全癌样本测序数据和在线工具分析了LEDGF/p75与预后、基因组不稳定性、DNA损伤修复、预后的可选择剪接、蛋白相互作用和肿瘤免疫之间的相关性。总结起来，本研究发现LEDGF/p75可能作为下丘脑皮质腺瘤癌、肾脏嗜铬细胞瘤、肝细胞癌、胰腺腺癌、皮肤黑色素瘤和清除细胞型肾细胞癌（ccRCC）等肿瘤的预后预测指标。此外，我们进行了体外实验和基因微阵列测序，探讨了LEDGF/p75在ccRCC中的功能，为非突变SETD2 ccRCC亚型的发病机制提供了新的见解。© 2023 年该作者发表于Research Network of Computational and Structural Biotechnology并由Elsevier B.V.出版。

Lens epithelium-derived growth factor (LEDGF/p75) is a reader of epigenetic marks and a potential target for therapeutic intervention. Its involvement in human immunodeficiency virus (HIV) integration and the development of leukemia driven by MLL (also known as KMT2A) gene fusion make it an attractive candidate for drug development. However, exploration of LEDGF/p75 as an epigenetic reader of H3K36me3 in tumors is limited. Here, for the first time, we analyze the role of LEDGF/p75 in multiple cancers via multiple online databases and in vitro experiments. We used pancancer bulk sequencing data and online tools to analyze correlations of LEDGF/p75 with prognosis, genomic instability, DNA damage repair, prognostic alternative splicing, protein interactions, and tumor immunity. In summary, the present study identified that LEDGF/p75 may serve as a prognostic predictor for tumors such as adrenocortical carcinoma, kidney chromophobe, liver hepatocellular carcinoma, pancreatic adenocarcinoma, skin cutaneous melanoma, and clear cell renal cell carcinoma (ccRCC). In addition, in vitro experiments and gene microarray sequencing were performed to explore the function of LEDGF/p75 in ccRCC, providing new insights into the pathogenesis of the nonmutated SETD2 ccRCC subtype.© 2023 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.