MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, Macao SAR, China.
Front Immunol. 2024 Sep 16;15:1460915. doi: 10.3389/fimmu.2024.1460915. eCollection 2024.
Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) is documented to regulate lipid metabolism in multiple cancers, landscape analysis of its implications in PRAD are still missing at present. Here, we conducted an analysis of diverse cancer datasets revealing elevated expression in the PRAD cohort at both mRNA and protein levels. Interestingly, the elevated expression was associated with promoter hypermethylation and genetic alterations, notably the L134V mutation. Integration of comprehensive tumor immunological and genomic data revealed a robust positive correlation between expression levels and the abundance of CD8 T cells and macrophages. Further analyses identified significant associations between expression and various immune markers in tumor microenvironment. Single-cell transcriptomic profiling unveiled differential expression patterns across distinct cell types within the prostate tumor microenvironment. The Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that enriched pathways were primarily related to lipid biosynthesis, cholesterol biosynthesis, endoplasmic reticulum membrane functions, and various metabolic pathways. Gene Set Enrichment Analysis highlighted the involvement of elevated expression in crucial cellular processes, including the cell cycle and biosynthesis of cofactors pathways. In functional studies, overexpression promoted the proliferation, metastasis and invasion of prostate cancer cells, whereas downregulation inhibits these processes. This study provides comprehensive insights into the multifaceted roles of SCD in PRAD pathogenesis, underscoring its potential as both a therapeutic target and prognostic biomarker.
前列腺腺癌 (PRAD) 是一种普遍存在的全球恶性肿瘤,与其他类型的癌症相比,它更依赖于脂代谢来促进肿瘤进展。虽然 Stearoyl-coenzyme A 去饱和酶 (SCD) 被证明可以调节多种癌症中的脂代谢,但目前在 PRAD 中其影响的全景分析仍然缺失。在这里,我们对各种癌症数据集进行了分析,揭示了在 PRAD 队列中 mRNA 和蛋白质水平上的 表达升高。有趣的是,这种升高的表达与 启动子超甲基化和遗传改变有关,特别是 L134V 突变。综合肿瘤免疫和基因组数据的整合揭示了 表达水平与 CD8 T 细胞和巨噬细胞丰度之间存在强大的正相关。进一步的分析确定了 表达与肿瘤微环境中各种免疫标志物之间的显著关联。单细胞转录组谱分析揭示了前列腺肿瘤微环境中不同细胞类型之间的 表达模式存在差异。基因本体论和京都基因与基因组百科全书分析表明, 富集的途径主要与脂质生物合成、胆固醇生物合成、内质网膜功能和各种代谢途径有关。基因集富集分析强调了 表达升高在关键细胞过程中的参与,包括细胞周期和辅因子生物合成途径。在功能研究中, 过表达促进了前列腺癌细胞的增殖、转移和侵袭,而下调则抑制了这些过程。这项研究提供了 SCD 在 PRAD 发病机制中多方面作用的全面见解,强调了它作为治疗靶点和预后生物标志物的潜力。
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