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结直肠腺癌中线粒体代谢相关分子亚型的特征及免疫浸润分析。

Characterization of mitochondrial metabolism related molecular subtypes and immune infiltration in colorectal adenocarcinoma.

机构信息

Department of Gastrointestinal Surgery, Central Hospital of Zibo, Zibo, China.

Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

Sci Rep. 2024 Oct 17;14(1):24326. doi: 10.1038/s41598-024-75482-2.

DOI:10.1038/s41598-024-75482-2
PMID:39414905
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11484867/
Abstract

Colorectal adenocarcinoma (COAD) is the most common subtype of colorectal cancer. Due to the imperfect prognosis of COAD, related prognostic factors and possible mechanisms need to be further investigated. During tumor development, mitochondria help tumor cells survive in a variety of ways, so that further screening of mitochondrial metabolism related targets has positive implications for COAD. We screened the mitochondrial metabolism-related genes (MMRG) associated with the COAD prognosis and explored the MMRG-related molecular subtype characteristics of by unsupervised consensus clustering analysis. Using ESTIMATE and ssGSEA algorithms, we evaluated the immunoinfiltration characteristic landscape of different molecular subtypes defined by MMRG. Combining the expression profiles of differentially expressed genes associated with the MMRG subgroup and the survival characteristics of COAD, we constructed an MMRG prognostic model using LASSO-univariate Cox analysis and successfully validated its impact on independently predicting risk stratification of COAD. The potential clinical value of the MMRG score was subsequently evaluated by subgroup immunoinfiltration characteristics and drug susceptibility prediction analysis. We also offer SEC11A as a new potential target for COAD by single-cell sequencing analysis. The effect of SEC11A on the proliferation, invasion abilities and mitochondrial dysfunction of COAD cells was confirmed through in vitro experiments. Our study provides new insights into the role of MMRG and new target for COAD potential intervention.

摘要

结直肠腺癌(COAD)是结直肠癌最常见的亚型。由于 COAD 的预后并不完善,因此需要进一步研究相关的预后因素和可能的机制。在肿瘤发展过程中,线粒体通过多种方式帮助肿瘤细胞存活,因此进一步筛选与线粒体代谢相关的靶点对 COAD 具有积极意义。我们筛选了与 COAD 预后相关的线粒体代谢相关基因(MMRG),并通过无监督共识聚类分析探讨了 MMRG 相关的分子亚型特征。利用 ESTIMATE 和 ssGSEA 算法,我们评估了不同 MMRG 定义的分子亚型的免疫浸润特征景观。结合与 MMRG 亚组相关的差异表达基因的表达谱和 COAD 的生存特征,我们使用 LASSO 单因素 Cox 分析构建了 MMRG 预后模型,并成功验证了其对独立预测 COAD 风险分层的影响。随后通过亚组免疫浸润特征和药物敏感性预测分析评估了 MMRG 评分的潜在临床价值。我们还通过单细胞测序分析为 COAD 提供了 SEC11A 作为新的潜在靶点。通过体外实验证实了 SEC11A 对 COAD 细胞增殖、侵袭能力和线粒体功能障碍的影响。我们的研究为 MMRG 的作用提供了新的见解,并为 COAD 的潜在干预提供了新的靶点。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/b7c421978eb6/41598_2024_75482_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/9770fd382529/41598_2024_75482_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/b5e89dbe5b2c/41598_2024_75482_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/996f5d8db774/41598_2024_75482_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/2ed3c6e4b114/41598_2024_75482_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/4702dfbc14ea/41598_2024_75482_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/9845062c9eab/41598_2024_75482_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/584a5c0dc774/41598_2024_75482_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0e/11484867/1c82b3c1414b/41598_2024_75482_Fig11_HTML.jpg

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本文引用的文献

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Mitochondrial function and gastrointestinal diseases.线粒体功能与胃肠道疾病。
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Identification and analysis of prognostic metabolic characteristics in colon adenocarcinoma.结肠腺癌预后代谢特征的鉴定与分析
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Osthole impairs mitochondrial metabolism and the autophagic flux in colorectal cancer.蛇床子素损害结直肠癌中的线粒体代谢和自噬通量。
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