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基于m6A阅读蛋白上调和免疫浸润构建多种恶性肿瘤预后模型

Development of a prognostic model based on m6A reader upregulation and immune infiltration in multiple malignant tumors.

作者信息

Han Yang, Xia Wei, Ma Zhong-Na, Mai Zhong-Chao, Ma Yu-Shui, Fu Da, Zhuang Juhua

机构信息

Department of Nuclear Medicine, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Nuclear Medicine, Pudong New Area Gongli Hospital, Shanghai, China.

出版信息

Transl Cancer Res. 2025 Jul 30;14(7):4219-4242. doi: 10.21037/tcr-2024-2616. Epub 2025 Jul 27.

Abstract

BACKGROUND

High expression has been previously observed in diverse tumor types. On this basis, the present work focused on exploring the effects of on pan-cancer occurrence and progression, as well as its potential functions and molecular regulatory mechanisms.

METHODS

gene expression, protein expression, Tumor Node Metastasis (TNM) stage, and survival prognosis in thirty-three different tumors across thirty-three tumors were analyzed via The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, which included 9,664 cancer tissues and 711 normal tissues, with R software (version 3.6.3). A series of bioinformatics analyses were performed to determine the relationships between the expression of -associated genes and prognosis, DNA promoter methylation, phosphorylation status and immune cell infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate gene functions. Cancer and corresponding para-cancerous samples were confirmed via immunohistochemistry.

RESULTS

This study confirmed that overexpression was associated with cancer development and a dismal prognosis in multiple types of cancer. Mutation and amplification were the main types of alterations in bladder urothelial carcinoma and esophageal adenocarcinoma, respectively. The phosphorylation and methylation levels of were linked to multiple tumor types. Furthermore, the expression level was positively correlated with infiltration degree in CESC, LIHC, HNSC-HPV, and MESO-associated fibroblasts in TCGA. In addition, nine Chinese herbal medicines and ten Chinese medicinal plant components targeting were identified.

CONCLUSIONS

affects tumor occurrence and progression. The expression of may serve as a reliable prognostic marker as well as a potential therapeutic target.

摘要

背景

此前已观察到其在多种肿瘤类型中高表达。在此基础上,本研究聚焦于探索其对泛癌发生发展的影响,以及潜在功能和分子调控机制。

方法

通过癌症基因组图谱(TCGA)和基因表达综合数据库(GEO),利用R软件(版本3.6.3)分析了33种不同肿瘤中该基因的表达、蛋白质表达、肿瘤淋巴结转移(TNM)分期及生存预后,其中包括9664例癌组织和711例正常组织。进行了一系列生物信息学分析,以确定该相关基因表达与预后、DNA启动子甲基化、磷酸化状态及免疫细胞浸润之间的关系。进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析以阐明基因功能。通过免疫组织化学对癌组织及相应癌旁组织样本进行确认。

结果

本研究证实该基因过表达与多种癌症的发生发展及不良预后相关。突变和扩增分别是膀胱尿路上皮癌和食管腺癌的主要改变类型。该基因的磷酸化和甲基化水平与多种肿瘤类型相关。此外,在TCGA数据库中,该基因表达水平与子宫颈鳞状细胞癌、肝癌、人乳头瘤病毒阳性的头颈部鳞状细胞癌及间皮瘤相关成纤维细胞中的浸润程度呈正相关。此外,还鉴定出了9种靶向该基因的中药和10种中药植物成分。

结论

该基因影响肿瘤的发生发展。其表达可作为可靠的预后标志物及潜在治疗靶点。

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