Construction and validation of consensus clustering-derived metabolism- and immune-associated genes model for prognosis prediction in cancer patients with liver metastases

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-07-12 DOI:10.1016/j.canlet.2025.217915

Jing Wu , Xinyao Qiu , Tao Zhou , Yani Zhang , Shuai Li , Ji Hu , Siyun Shen , Lei Chen , Yingcheng Yang , Shuai Yang , Hongyang Wang

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引用次数: 0

Abstract

Liver metastasis (LM) is a cancer hallmark linked to poor prognosis and high mortality. Immune and metabolic shifts play critical roles in LM progression. This study aims to explore the prognostic value of immune- and metabolism-associated genes for LM and investigate their potential mechanisms. Here, we established a prognostic model based on Consensus Clustering-derived Metabolism- and Immune-associated genes (CCMI). Both the CCMI model and each hub gene demonstrated predictive value for LM patients at RNA and protein levels. Moreover, patients with high CCMI scores showed worse prognosis, elevated mutation frequency and heterogeneity, enrichment of cancer-promoting pathways, and increased neutrophil infiltration. Mechanistically, functional studies showed that CKB and ARG2 enhanced the proliferation, self-renewal, migration and invasion of cancer cells via activating MAPK or PI3K-AKT signaling pathways. MAFF was validated to play a key role in inducing neutrophil recruitment and infiltration through upregulating expression of CXCL1, thereby accelerating LM progression. In conclusion, this study presented a practical prognostic CCMI model for LM patients and investigated associated molecular and immune signatures. Our results uncovered the regulatory mechanisms of CCMI hub genes that promote LM progression, highlighting their potential as biomarkers for precision diagnosis and treatment of LM.

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一致聚类衍生的代谢和免疫相关基因模型的构建和验证用于肝癌转移患者预后预测

肝转移（LM）是与预后差和高死亡率相关的癌症标志。免疫和代谢变化在LM进展中起关键作用。本研究旨在探讨免疫和代谢相关基因对LM的预后价值，并探讨其潜在机制。在这里，我们建立了一个基于共识聚类衍生代谢和免疫相关基因（CCMI）的预后模型。CCMI模型和每个中心基因在RNA和蛋白质水平上都显示出对LM患者的预测价值。此外，CCMI评分高的患者预后较差，突变频率和异质性升高，促癌途径富集，中性粒细胞浸润增加。在机制上，功能研究表明CKB和ARG2通过激活MAPK或PI3K-AKT信号通路增强癌细胞的增殖、自我更新、迁移和侵袭。MAFF通过上调CXCL1的表达，在诱导中性粒细胞募集和浸润中发挥关键作用，从而加速LM的进展。总之，本研究提出了一个实用的LM患者预后CCMI模型，并研究了相关的分子和免疫特征。我们的研究结果揭示了CCMI中心基因促进LM进展的调控机制，突出了它们作为LM精确诊断和治疗的生物标志物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.