Characteristics, clinical significance, and cancer immune interactions of lipid metabolism in prostate cancer.

IF 1.5 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2024-07-31 Epub Date: 2024-07-26 DOI:10.21037/tcr-23-2140

Zhipeng Xu, Xu Xu, Jianpeng Hu, Jian Tan, Yuanye Wan, Feilun Cui

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引用次数: 0

Abstract

Background: The relationship between lipid metabolism, immune response, and immunotherapy in prostate cancer (PCa) is closely intertwined, and targeted intervention in lipid metabolism may facilitate the success of anticancer immunotherapy. This research attempted to explore effective immunotherapy for PCa.

Methods: We obtained RNA sequencing (RNA-seq) data for PCa patients from the UCSC Xena platform. Data analysis of differentially expressed genes (DEGs) was performed using package limma in R. Then, DEGs were subjected to enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The Human Protein Atlas (HPA) database was conducted to validate the protein expression of the up-regulated lipid metabolism related genes (LMRGs) between PCa tissues and normal prostate tissues. And then we identified critical transcription factors (TFs), LMRGs and miRNA by constructing a regulatory network of TF-gene-miRNA. Furthermore, we determined the high and low groups based on the score of lipid metabolism enrichment. The hallmark gene sets were derived from gene expression profiles using the gene set variation analysis (GSVA) R package. Finally, we conducted immune infiltration analysis and drug sensitivity analysis.

Results: Immune response and lipid metabolism have undergone significant changes in PCa and paracancerous tissues compared to normal tissues. A total of 21 LMRGs were differentially up-regulated in PCa. The TF-gene-miRNA network showed that PLA2G7, TWIST1, and TRIB3 may be the key genes that elevated lipid metabolism in PCa. The high group had more infiltration of B cell memory, macrophage M0, macrophage M1, and myeloid dendritic cell resting, and the low group had more infiltration of B cell plasma, monocyte, myeloid dendritic cell activated, and mast cell resting. The majority of checkpoint genes exhibited high expression levels in the low group. Lipid metabolism was remarkedly correlated with drug sensitivity.

Conclusions: The analysis of lipid metabolism and related genes has revealed a complex regulatory mechanism that has a significant influence on immune response, immunotherapy, and medication guidance for patients with PCa.

Keywords: Prostate cancer (PCa); lipid metabolism; cancer immune; RNA sequencing (RNA-seq).

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前列腺癌脂质代谢的特点、临床意义和癌症免疫相互作用。

背景：前列腺癌（PCa）的脂质代谢、免疫反应和免疫治疗之间的关系密切，有针对性地干预脂质代谢可能有助于抗癌免疫治疗的成功。本研究试图探索有效的 PCa 免疫疗法：我们从 UCSC Xena 平台获得了 PCa 患者的 RNA 测序（RNA-seq）数据。然后，对差异表达基因（DEGs）进行基因本体（GO）和京都基因组百科全书（KEGG）通路的富集分析。人类蛋白质图谱（HPA）数据库验证了PCa组织与正常前列腺组织之间上调的脂质代谢相关基因（LMRGs）的蛋白质表达。然后，我们通过构建TF-基因-miRNA的调控网络，确定了关键转录因子（TFs）、LMRGs和miRNA。此外，我们还根据脂质代谢富集的得分确定了高分组和低分组。标志基因集是利用基因集变异分析（GSVA）R软件包从基因表达谱中得出的。最后，我们进行了免疫浸润分析和药物敏感性分析：结果：与正常组织相比，PCa 和癌旁组织的免疫反应和脂质代谢发生了显著变化。共有21个LMRGs在PCa中被差异上调。TF-基因-miRNA网络显示，PLA2G7、TWIST1和TRIB3可能是PCa脂质代谢升高的关键基因。研究还发现，在PCa中，B细胞记忆、巨噬细胞M0、巨噬细胞M1和髓系树突状细胞静息浸润较多，而B细胞浆、单核细胞、髓系树突状细胞激活和肥大细胞静息浸润较多。大多数检查点基因在低水平组中表现出较高的表达水平。脂质代谢与药物敏感性显著相关：脂质代谢及相关基因的分析揭示了一种复杂的调控机制，对PCa患者的免疫反应、免疫治疗和用药指导具有重要影响：前列腺癌（PCa）；脂质代谢；癌症免疫；RNA测序（RNA-seq）。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.