Expression, Prognostic Value, and Biological Function of CENPM in Colon Adenocarcinoma.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zhiming Cai, Zhenrong Yang, Qian Yu, Tao Lin, Xincheng Su, Lv Lin, Yongjian Zhou
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引用次数: 0

Abstract

Introduction: Centromere protein M (CENPM), a member of the CENP family, is correlated with several malignancies, but its role in colon adenocarcinoma (COAD) is unclear. This study aims to explore the expression, prognostic significance, and biological role of CENPM in COAD.

Methods: The association of CENPM with the occurrence and progression of COAD was thoroughly analyzed via several bioinformatics databases. Furthermore, the correlation between CENPM expression and clinicopathological features and prognostic value was validated via immunohistochemistry (IHC) of tissue microarrays (TMAs) from 80 patients.

Results: CENPM mRNA expression was significantly elevated in COAD samples compared with healthy tissues. As COAD progressed, CENPM expression decreased, and patients with lower CENPM transcript levels had a worse prognosis. IHC results further confirmed the overexpression of CENPM in COAD patients, identifying this gene as an independent prognostic factor. Additionally, high CENPM expression was linked to methylation in COAD patients, and the primary function of CENPM and its neighboring genes was determined to be cell cycle regulation. Immunological analysis demonstrated that CENPM expression was positively correlated with activated CD8+ T cells, CD4+ T cells, and dendritic cells (DCs) but negatively correlated with regulatory T cells (Tregs). CENPM expression was positively correlated with that of the immune checkpoint genes LAG3, CD244, LGALS9, PDCD1 (PD1), and PVRL2 but negatively correlated with the expression of BTLA, CSF1R, KDR, IL10RB, PDCD1LG2, and TGFBR1.

Conclusion: CENPM is an independent prognostic factor for COAD, with its overexpression associated with improved survival. It regulates the cell cycle and tumor microenvironment, making it a promising potential predictive biomarker for immune therapy response.

CENPM在结肠腺癌中的表达、预后价值及生物学功能。
着丝粒蛋白M (CENPM)是CENP家族的一员,与多种恶性肿瘤相关,但其在结肠腺癌(COAD)中的作用尚不清楚。本研究旨在探讨CENPM在COAD中的表达、预后意义及生物学作用。方法:通过多个生物信息学数据库深入分析CENPM与COAD发生发展的关系。此外,通过组织微阵列(tma)的免疫组化(IHC)验证了80例患者的CENPM表达与临床病理特征和预后价值之间的相关性。结果:与健康组织相比,COAD样品中CENPM mRNA表达显著升高。随着COAD的进展,CENPM的表达减少,而低CENPM转录物水平的患者预后较差。IHC结果进一步证实了COAD患者中CENPM的过表达,确定该基因是一个独立的预后因素。此外,在COAD患者中,高CENPM表达与甲基化有关,并且确定了CENPM及其邻近基因的主要功能是细胞周期调节。免疫学分析表明,CENPM的表达与活化的CD8+ T细胞、CD4+ T细胞和树突状细胞(dc)呈正相关,而与调节性T细胞(Tregs)负相关。CENPM的表达与免疫检查点基因LAG3、CD244、LGALS9、PDCD1 (PD1)、PVRL2呈正相关,与BTLA、CSF1R、KDR、IL10RB、PDCD1LG2、TGFBR1的表达呈负相关。结论:CENPM是COAD的独立预后因素,其过表达与生存率提高相关。它调节细胞周期和肿瘤微环境,使其成为一种有前景的潜在预测免疫治疗反应的生物标志物。
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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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