癌症铜中毒相关亚型的鉴定及肿瘤微环境特征

IF 0.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Precision Medical Sciences Pub Date : 2023-05-21 DOI:10.1002/prm2.12101
Hao Han, Ye Jin, Haihao Yan, Zheng Liu
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引用次数: 0

摘要

铜中毒是一种受调控的细胞死亡,其特征是细胞中过量铜的致命积累。然而,它在结肠腺癌(COAD)中的作用仍然难以捉摸。我们的研究旨在解读COAD患者铜中毒相关基因(CRG)的生物学功能。表达数据来自癌症基因组图谱,而基因表达综合数据库用于验证结果。共从COAD患者中选择了8个差异表达的CRG。随后,将患者分为三种具有不同临床和生物学特征的亚型。鉴于A和C亚型之间预后的巨大差异,我们选择它们进行进一步研究,包括临床进展、致癌途径和免疫细胞浸润的变化。为了更好地评估,我们还建立了铜中毒指数(CI)来量化CRGs表达的异质性。富集分析表明,高CI组在免疫激活途径中富集。同时,高CI组的免疫抑制细胞浸润和免疫检查点升高。我们构建的CI在不同的临床组中具有预测功能。此外,我们注意到CRG,尤其是CDKN2A,与COAD患者的临床进展和肿瘤中的免疫细胞浸润密切相关。此外,CDKN2A可能成为COAD背景下免疫治疗的潜在新靶点。
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Identification of cuproptosis‐related subtypes and tumor microenvironment characteristics in colon cancer
Cuproptosis is a form of regulated cell death, which is characterized by the lethal accumulation of excessive copper in cells. However, its role in colon adenocarcinoma (COAD) remains elusive. Our study aimed to decipher the biological function of cuproptosis‐related genes (CRGs) in patients with COAD. The expression data were obtained from The Cancer Genome Atlas, while the Gene Expression Omnibus database was used to verify the results. A total of eight differentially expressed CRGs were selected from patients with COAD. Subsequently, patients were stratified into three subtypes with distinct clinical and biological features. In view of the huge differences in the prognosis between subtypes A and C, we selected them for further study, including the variations in clinical progressions, oncogenic pathways, and immune cell infiltration. For the sake of better evaluation, we also established a cuproptosis index (CI) to quantify the heterogeneity of CRGs expression. Enrichment analysis showed that the high‐CI group was enriched in immune activation pathways. Meanwhile, the immunosuppressive cell infiltration and immune checkpoints were elevated in the high‐CI group. The CI we constructed had its predicting function in different clinical groups. Besides, we noticed that CRGs, especially CDKN2A, were closely related to the clinical progression in patients with COAD and immune cell infiltration in tumors. Moreover, CDKN2A could become a potential novel target for immunotherapy in the setting of COAD.
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来源期刊
Precision Medical Sciences
Precision Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-
自引率
0.00%
发文量
33
审稿时长
15 weeks
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