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鉴定和验证基底膜相关基因 AGRN 作为结直肠癌患者的预后和免疫相关生物标志物。

Identification and validation of basement membrane-associated gene AGRN as prognostic and immune-associated biomarkers in colorectal cancer patients.

机构信息

Department of General Surgery Sciences, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.

Emergency Department of First Hospital Affiliated to Hebei Medical University, Shijiazhuang, China.

出版信息

J Cell Mol Med. 2024 Aug;28(16):e70010. doi: 10.1111/jcmm.70010.

DOI:10.1111/jcmm.70010
PMID:39183444
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11345205/
Abstract

Colorectal cancer (COCA) has a poor prognosis, with growing evidence implicating basement membranes (BMs) in cancer progression. Our goal was to investigate the role and predictive significance of BMs in COCA patients. We obtained BMs-related genes from cutting-edge research and used TCGA and GTEx databases for mRNA expression and patient information. Cox regression and LASSO regression were used for prognostic gene selection and risk model construction. We compared prognosis using Kaplan-Meier analysis and examined drug sensitivity differences. The CMAP dataset identified potential small molecule drugs. In vitro tests involved suppressing a crucial gene to observe its impact on tumour metastasis. We developed a 12 BMs-based approach, finding it to be an independent prognostic factor. Functional analysis showed BMs concentrated in cancer-associated pathways, correlating with immune cell infiltration and immune checkpoint activation. High-risk individuals exhibited increased drug sensitivity. AGRN levels were linked to decreased progression-free survival (p < 0.001). AGRN knockdown suppressed tumour growth and metastasis. Our study offers new perspectives on BMs in COCA, concluding that AGRN is a dependable biomarker for patient survival and prognosis.

摘要

结直肠癌（COCA）预后较差，越来越多的证据表明基底膜（BMs）在癌症进展中起作用。我们的目标是研究 BMs 在 COCA 患者中的作用和预测意义。我们从最新研究中获得了与 BMs 相关的基因，并使用 TCGA 和 GTEx 数据库获取 mRNA 表达和患者信息。Cox 回归和 LASSO 回归用于预后基因选择和风险模型构建。我们通过 Kaplan-Meier 分析比较了预后，并检查了药物敏感性差异。CMAP 数据集确定了潜在的小分子药物。体外试验涉及抑制关键基因，观察其对肿瘤转移的影响。我们开发了一种基于 12 个 BMs 的方法，发现它是一个独立的预后因素。功能分析表明 BMs 集中在与癌症相关的通路中，与免疫细胞浸润和免疫检查点激活相关。高风险个体表现出更高的药物敏感性。AGRN 水平与无进展生存期缩短相关（p<0.001）。AGRN 敲低抑制肿瘤生长和转移。我们的研究为 COCA 中的 BMs 提供了新的视角，结论是 AGRN 是患者生存和预后的可靠生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/f79376622f15/JCMM-28-e70010-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/901f01c55c3a/JCMM-28-e70010-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/f79376622f15/JCMM-28-e70010-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/dd04c086a837/JCMM-28-e70010-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/bdfd1d004201/JCMM-28-e70010-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/631d89fbd86d/JCMM-28-e70010-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/53a47cdb1f29/JCMM-28-e70010-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/8a5f49a2b8e3/JCMM-28-e70010-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/901f01c55c3a/JCMM-28-e70010-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d50/11345205/f79376622f15/JCMM-28-e70010-g002.jpg

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