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用于预测结直肠癌总生存期和免疫反应的中心预后模型。

-Centric Prognostic Model for Predicting Overall Survival and Immune Response in Colorectal Cancer.

机构信息

Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin 300071, China.

College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.

出版信息

Genes (Basel). 2024 Aug 29;15(9):1139. doi: 10.3390/genes15091139.

DOI:10.3390/genes15091139
PMID:39336730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11430869/
Abstract

Colorectal cancer (CRC), a prevalent malignancy, ranks third in global incidence and second in mortality rates. Despite advances in screening methods such as colonoscopy, the accurate diagnosis of CRC remains challenging due to the absence of reliable biomarkers. This study aimed to develop a robust prognostic model for precise CRC outcome prediction. Employing weighted co-expression network analysis (WGCNA) and Cox regression analysis on data from The Cancer Genome Atlas (TCGA), we identified a panel of 12 genes strongly associated with patient survival. This gene panel facilitated accurate CRC outcome predictions, which is also validated via the external validation cohort GSE17536. We conducted further investigations into the key gene, (), using single-cell transcriptomic data and immune infiltration analysis in CRC patients. Our results revealed a significant correlation between high expression and the reduced prevalence of key immune cells, including B cells, CD4+ cytotoxic T cells, CD8+ T cells, and NKT cells. Functional experiments showed that gene interference in the CRC cell lines significantly decreased cancer cell proliferation, underscoring 's role in intestinal immunity modulation. The -centric prognostic model developed enhances prognosis prediction accuracy and offers critical insights for CRC diagnosis and therapeutic interventions.

摘要

结直肠癌(CRC)是一种常见的恶性肿瘤,其发病率全球排名第三,死亡率全球排名第二。尽管筛查方法如结肠镜检查有所进步,但由于缺乏可靠的生物标志物,CRC 的准确诊断仍然具有挑战性。本研究旨在开发一种稳健的预后模型,以精确预测 CRC 的结果。我们使用加权共表达网络分析(WGCNA)和来自癌症基因组图谱(TCGA)的数据的 Cox 回归分析,确定了一组与患者生存强烈相关的 12 个基因。该基因面板可实现对 CRC 结果的准确预测,这也通过外部验证队列 GSE17536 得到了验证。我们使用 CRC 患者的单细胞转录组数据和免疫浸润分析进一步研究了关键基因 ()。我们的结果表明,高表达与关键免疫细胞(包括 B 细胞、CD4+细胞毒性 T 细胞、CD8+T 细胞和 NKT 细胞)的减少患病率之间存在显著相关性。功能实验表明,CRC 细胞系中基因干扰显著降低了癌细胞的增殖,突出了基因在肠道免疫调节中的作用。基于的预后模型可提高预后预测的准确性,并为 CRC 的诊断和治疗干预提供重要见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/205b8c557c97/genes-15-01139-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/8e3326e8e9dd/genes-15-01139-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/be9286560ce3/genes-15-01139-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/3fe51b7feee4/genes-15-01139-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/4632474237ea/genes-15-01139-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/d564cc2988bc/genes-15-01139-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/205b8c557c97/genes-15-01139-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/8e3326e8e9dd/genes-15-01139-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/be9286560ce3/genes-15-01139-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/3fe51b7feee4/genes-15-01139-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/4632474237ea/genes-15-01139-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/d564cc2988bc/genes-15-01139-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a956/11430869/205b8c557c97/genes-15-01139-g006.jpg

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本文引用的文献

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Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy.脂肪酸代谢相关基因在结直肠癌中的预后价值及其对免疫治疗的潜在意义。
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Exploration and validation of a combined immune and metabolism gene signature for prognosis prediction of colorectal cancer.
联合免疫和代谢基因特征探索及其在结直肠癌预后预测中的验证。
Front Endocrinol (Lausanne). 2022 Nov 28;13:1069528. doi: 10.3389/fendo.2022.1069528. eCollection 2022.
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