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,,和在结肠腺癌中的预后意义:一种多组学和单细胞方法

Prognostic Significance of , , and in Colon Adenocarcinoma: A Multi-Omics and Single-Cell Approach.

作者信息

Cheon Jaehwan, Kim Sang Hyun, Park Jaehyung, Kim Tae Hoon

机构信息

Department of Otorhinolaryngology-Head & Neck Surgery, Korea University College of Medicine, Anam-ro 145, Seongbuk-gu, Seoul 02841, Republic of Korea.

Department of Biomedical Science, Korea University College of Medicine, Anam-ro 145, Seongbuk-gu, Seoul 02841, Republic of Korea.

出版信息

Biomedicines. 2025 Apr 24;13(5):1035. doi: 10.3390/biomedicines13051035.

DOI:10.3390/biomedicines13051035
PMID:40426863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12108730/
Abstract

: Colon adenocarcinoma (COAD), the most prevalent form of colorectal cancer, remains a leading cause of cancer-related mortality. Advances in various treatments for COAD have significantly improved treatment outcomes. However, therapeutic limitations persist, highlighting the need for personalized strategies driven by novel biomarkers. The aim was to identify key hub genes that could be potential biomarkers of COAD using comprehensive bioinformatic analyses. : Differentially expressed genes (DEGs) and co-DEGs were identified from COAD gene expression datasets. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Hub genes were extracted from protein-protein interaction (PPI) networks and validated epigenetically using microRNA (miRNA) and DNA methylation datasets. Their expression patterns were further examined via single-cell RNA sequencing (scRNA-seq) and immune cell infiltration analysis. Prognostic relevance was assessed based on tumor metastasis and survival outcomes. : Gene expression profiling identified 118 co-DEGs, with GO and KEGG pathway analyses revealing significant pathway enrichment. PPI network analysis pinpointed 27 key co-DEGs. Epigenetic profiling indicated that both miRNA interference and DNA methylation regulate , , and expression levels. scRNA-seq analysis showed elevated expression in epithelial cells and in myeloid cells, and reduced expression in stromal cells. Prognostic analysis further demonstrated that and are significantly associated with poor COAD outcomes. : We identified some potential prognostic biomarkers for patients with COAD. Further experimental validation is required to translate these findings into precision medicine for COAD.

摘要

结肠癌(COAD)是结直肠癌最常见的形式,仍然是癌症相关死亡的主要原因。COAD各种治疗方法的进展显著改善了治疗效果。然而,治疗局限性仍然存在,这突出了由新型生物标志物驱动的个性化策略的必要性。目的是通过全面的生物信息学分析确定可能成为COAD潜在生物标志物的关键枢纽基因。

从COAD基因表达数据集中鉴定差异表达基因(DEG)和共差异表达基因(co-DEG)。进行了功能富集分析,包括基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析。从蛋白质-蛋白质相互作用(PPI)网络中提取枢纽基因,并使用微RNA(miRNA)和DNA甲基化数据集进行表观遗传学验证。通过单细胞RNA测序(scRNA-seq)和免疫细胞浸润分析进一步检查它们的表达模式。基于肿瘤转移和生存结果评估预后相关性。

基因表达谱分析鉴定出118个共差异表达基因,GO和KEGG通路分析显示有显著的通路富集。PPI网络分析确定了27个关键共差异表达基因。表观遗传学分析表明,miRNA干扰和DNA甲基化均调节 、 和 的表达水平。scRNA-seq分析显示上皮细胞中 表达升高,髓样细胞中 表达升高,基质细胞中 表达降低。预后分析进一步表明, 和 与COAD不良预后显著相关。

我们为COAD患者鉴定了一些潜在的预后生物标志物。需要进一步的实验验证,以将这些发现转化为COAD的精准医学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/82d741dba9ab/biomedicines-13-01035-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/c56481049fc8/biomedicines-13-01035-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/82d741dba9ab/biomedicines-13-01035-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/c56481049fc8/biomedicines-13-01035-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/61c18125a50e/biomedicines-13-01035-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/59063a70554d/biomedicines-13-01035-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/e3ee132885f0/biomedicines-13-01035-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/c4d378bd6741/biomedicines-13-01035-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/67a10cf1ed98/biomedicines-13-01035-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a5/12108730/82d741dba9ab/biomedicines-13-01035-g008.jpg

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本文引用的文献

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Colorectal Cancer: Current Updates and Future Perspectives.结直肠癌:当前进展与未来展望
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Claudins-Promising Biomarkers for Selected Gastrointestinal (GI) Malignancies?紧密连接蛋白——某些胃肠道恶性肿瘤有前景的生物标志物?
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Claudin-1 interacts with EPHA2 to promote cancer stemness and chemoresistance in colorectal cancer.Claudin-1 与 EPHA2 相互作用,促进结直肠癌中的癌症干细胞特性和化疗耐药性。
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Targeting the tumor microenvironment: Potential strategy for cancer therapeutics.靶向肿瘤微环境:癌症治疗的潜在策略。
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Improving the response to oxaliplatin by targeting chemotherapy-induced CLDN1 in resistant metastatic colorectal cancer cells.通过靶向化疗诱导的紧密连接蛋白1改善耐药转移性结直肠癌细胞对奥沙利铂的反应。
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The expression of SERPINE1 in colon cancer and its regulatory network and prognostic value.丝氨酸蛋白酶抑制剂 1 在结肠癌中的表达及其调控网络和预后价值。
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