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结合加权相关基因网络分析和单细胞测序探索前列腺癌微环境中免疫细胞之间的相互作用:一项综合生物信息学分析

Exploring the interaction between immune cells in the prostate cancer microenvironment combining weighted correlation gene network analysis and single-cell sequencing: An integrated bioinformatics analysis.

作者信息

Hashemi Karoii Danial, Bavandi Sobhan, Djamali Melika, Abroudi Ali Shakeri

机构信息

Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Department of Biology, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran.

出版信息

Discov Oncol. 2024 Sep 30;15(1):513. doi: 10.1007/s12672-024-01399-x.

DOI:10.1007/s12672-024-01399-x
PMID:39349877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11442730/
Abstract

BACKGROUND

The rise of treatment resistance and variability across malignant profiles has made precision oncology an imperative in today's medical landscape. Prostate cancer is a prevalent form of cancer in males, characterized by significant diversity in both genomic and clinical characteristics. The tumor microenvironment consists of stroma, tumor cells, and various immune cells. The stromal components and tumor cells engage in mutual communication and facilitate the development of a low-oxygen and pro-cancer milieu by producing cytokines and activating pro-inflammatory signaling pathways.

METHODS

In order to discover new genes associated with tumor cells that interact and facilitate a hypoxic environment in prostate cancer, we conducted a cutting-edge bioinformatics investigation. This included analyzing high-throughput genomic datasets obtained from the cancer genome atlas (TCGA).

RESULTS

A combination of weighted gene co-expression network analysis and single-cell sequencing has identified nine dysregulated immune hub genes (AMACR, KCNN3, MME, EGFR, FLT1, GDF15, KDR, IGF1, and KRT7) that are believed to have significant involvement in the biological pathways involved with the advancement of prostate cancer enviriment. In the prostate cancer environment, we observed the overexpression of GDF15 and KRT7 genes, as well as the downregulation of other genes. Additionally, the cBioPortal platform was used to investigate the frequency of alterations in the genes and their effects on the survival of the patients. The Kaplan-Meier survival analysis indicated that the changes in the candidate genes were associated with a reduction in the overall survival of the patients.

CONCLUSIONS

In summary, the findings indicate that studying the genes and their genomic changes may be used to develop precise treatments for prostate cancer. This approach involves early detection and targeted therapy.

摘要

背景

治疗耐药性的增加以及恶性肿瘤特征的变异性使得精准肿瘤学在当今医学领域成为当务之急。前列腺癌是男性中一种常见的癌症形式,其基因组和临床特征具有显著的多样性。肿瘤微环境由基质、肿瘤细胞和各种免疫细胞组成。基质成分和肿瘤细胞相互交流,并通过产生细胞因子和激活促炎信号通路来促进低氧和促癌环境的形成。

方法

为了发现与前列腺癌中相互作用并促进低氧环境的肿瘤细胞相关的新基因,我们进行了一项前沿的生物信息学研究。这包括分析从癌症基因组图谱(TCGA)获得的高通量基因组数据集。

结果

加权基因共表达网络分析和单细胞测序相结合,确定了九个失调的免疫枢纽基因(AMACR、KCNN3、MME、EGFR、FLT1、GDF15、KDR、IGF1和KRT7),据信这些基因在与前列腺癌环境进展相关的生物学途径中具有重要作用。在前列腺癌环境中,我们观察到GDF15和KRT7基因的过表达以及其他基因的下调。此外,利用cBioPortal平台研究了这些基因的改变频率及其对患者生存的影响。Kaplan-Meier生存分析表明,候选基因的变化与患者总生存期的降低有关。

结论

总之,研究结果表明,研究这些基因及其基因组变化可用于开发前列腺癌的精准治疗方法。这种方法包括早期检测和靶向治疗。

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