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The involvement of high succinylation modification in the development of prostate cancer

琥珀酰化 三四脯氨酸 癌症研究 前列腺癌 癌症 病态的 癌变 基因表达 生物 信使核糖核酸 基因 计算生物学 病理 医学 生物化学 非翻译区 遗传学 乙酰化
作者
Zhenyang Zhang,Yanru Chen,Lingyu Fang,Jiang Zhao,Shishan Deng
出处
期刊:Frontiers in Oncology [Frontiers Media]
卷期号:12 被引量:15
标识
DOI:10.3389/fonc.2022.1034605
摘要

Succinylation modification of the lysine site plays an important role in tumorigenesis and development, but it is rarely reported in prostate cancer (PCa), so this study aims to elucidate its expression in and clinical correlation with PCa.A total of 95 tumor, 3 normal and 52 paired adjacent tissue of PCa were involved for succinylation stanning. 498 PCa samples with 20 succinylation modification-related genes from TCGA were downloaded for model construction. Statistical methods were employed to analyze the data, including Non-Negative Matrix Factorization (NMF) algorithm, t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm and Cox regression analysis.The pan-succinyllysine antibody stanning indicated that tumor tissues showed higher succinyllysine level than adjacent tissues (p<0.001). Gleason grade and PDL1 expression levels were significantly different (p<0.001) among the high, medium and low succinylation staining scores. The types of PCa tissue were divided into four clusters using RNA-seq data of 20 succinylation-related genes in TCGA database. Clinical characterize of age, PSA level, and pathological stage showed differences among four clusters. The expression of succinylation-related genes (KAT5, SDHD and GLYATL1) and PCa related genes (PDL1, AR and TP53) were significantly different in 52 matched tumor and adjacent tissues (p<0.001). GLYATL1 and AR gene expression was significantly related to the pathological stage of PCa.Succinylation was significantly increased in PCa tissues and was closely related to Gleason grade and PD-L1 expression. Model construction of 20 genes related to succinylation modification showed that the later the pathological stage of PCa, the higher the level of succinylation modification.
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