乳酸代谢亚型分析发现 CCDC80 是胃癌的新型预后生物标记物

IF 3.3 3区 医学 Q2 ONCOLOGY
Journal of Cancer Pub Date : 2024-08-26 eCollection Date: 2024-01-01 DOI:10.7150/jca.97640
Xiang Li, Yaqi Du
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引用次数: 0

摘要

乳酸代谢在肿瘤进展过程中起着至关重要的作用。目前,胃癌(GC)的预后较差。因此,我们的研究旨在调查与患者乳酸代谢相关的新型生物标记物。我们根据乳酸代谢相关基因(LMRGs)的表达情况,将癌症基因组图谱(TCGA)和基因表达总库(GEO)数据库中的患者数据分为不同亚型。根据这些亚型,我们确定了含盘旋卷曲结构域 80(CCDC80)作为进一步研究的对象。我们建立了单变量和多变量 Cox 回归模型,以确定 CCDC80 在 GC 中的预后价值。我们利用基因组富集分析(GSEA)进一步探讨了 CCDC80 影响 GC 预后的机制。我们还进行了免疫浸润和药物敏感性分析。最后,免疫组化染色被用来评估 CCDC80 在正常组织和肿瘤组织中的表达。我们观察到 CCDC80 在 GC 样本中过表达,并与 T 期和病理分期显著相关。多变量 Cox 分析确定 CCDC80 的高表达是一个独立的预后标志物。GSEA表明,氧化磷酸化途径在CCDC80低表达组中高度富集。此外,CCDC80 与免疫细胞浸润有关,尤其是 M2 巨噬细胞。CCDC80 表达较高的患者对紫杉醇的敏感性较低。总之,我们的研究结果表明,CCDC80是GC进展和免疫反应的关键调节因子,与乳酸代谢有关,可作为一种新型生物标记物用于预后和化疗治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lactate Metabolism Subtypes Analysis Reveals CCDC80 as a Novel Prognostic Biomarker in Gastric Cancer.

Lactate metabolism plays a vital role in tumor progression. Currently, gastric cancer (GC) has a poor prognosis. Therefore, our research aimed to investigate novel biomarkers related to lactate metabolism in patients. Patient data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were divided into subtypes based on the expression of lactate metabolism-related genes (LMRGs). Based on the subtypes, we identified coiled-coil domain containing 80 (CCDC80) for further investigation. Univariate and multivariate Cox regression models were constructed to determine the prognostic value of CCDC80 in GC. We further explored the mechanism by which CCDC80 affects GC prognosis using gene set enrichment analysis (GSEA). Immune infiltration and drug sensitivity analyses were also performed. Finally, immunohistochemical staining was used to evaluate CCDC80 expression in normal and tumor tissues. We observed that CCDC80 was overexpressed in GC samples and was significantly associated with T and pathological stages. Multivariate Cox analysis identified high CCDC80 expression as an independent prognostic marker. GSEA indicated that the oxidative phosphorylation pathway was highly enriched in the low CCDC80 expression group. Moreover, CCDC80 was associated with immune cell infiltration, especially that of M2 macrophages. Patients with higher CCDC80 expression exhibited lower sensitivity to paclitaxel. In conclusion, our findings demonstrate that CCDC80 is a critical regulator in GC progression and immune response and is associated with lactate metabolism, and it could be used as a novel biomarker for prognostic and chemotherapy treatment purposes.

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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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