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TIPE2与免疫细胞浸润相结合可预测结直肠癌的预后。

TIPE2 combined with immune cell infiltration predicts prognosis in colorectal cancer.

作者信息

Xia Hengbo, Pang Qingqing, Xu Aman, Hu Jie

机构信息

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, China.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, China.

出版信息

Sci Rep. 2025 Jul 31;15(1):27954. doi: 10.1038/s41598-025-10449-5.

DOI:10.1038/s41598-025-10449-5
PMID:40745253
Abstract

The incidence of colorectal cancer has shown an obvious upward trend worldwide. The prognostic prediction of CRC has not been well established. Based on immunohistochemistry staining, the expression and scoring of TIPE2 and CD8, CD20, and CD66b were evaluated and grouped. The clinicopathological parameters and IHC scores were analyzed and showed by Kaplan-Meier plots. High TIPE2 expression in CRC and normal tissues correlated with a better OS. In contrast, high CD8 and CD20 expression in CRC and normal tissues correlated with a worse OS. High CD66b expression in normal tissues was associated with a worse OS. Lasso and Cox analysis showed that N-stage, CA199, and CD8 in adjacent normal tissues were independent risk factors for OS. Grade and TIPE2 expression in cancer tissues were independent protective factors for OS in CRC patients. Moreover, the nomogram was constructed to predict the 1-, 3- and 5-year overall survival and validated by the calibration curves, receiver operating characteristic curves and decision curve analysis curves. Correlation analysis revealed that TIPE2 and CD8 were positively associated with PD-1 and TIM-3, indicating a potential link between TIPE2 and T cell exhaustion in colorectal cancer. TIPE2 combined with immune markers such as CD8, CD20, and CD66b in the TME can be used as biomarkers of disease progression and prognosis in CRC patients.

摘要

全球范围内,结直肠癌的发病率呈明显上升趋势。结直肠癌的预后预测尚未完全确立。基于免疫组织化学染色,对TIPE2以及CD8、CD20和CD66b的表达及评分进行评估并分组。分析临床病理参数和免疫组化评分,并通过Kaplan-Meier曲线展示。结直肠癌组织和正常组织中TIPE2高表达与较好的总生存期相关。相反,结直肠癌组织和正常组织中CD8和CD20高表达与较差的总生存期相关。正常组织中CD66b高表达与较差的总生存期相关。套索分析和Cox分析表明,N分期、CA199以及癌旁正常组织中的CD8是总生存期的独立危险因素。肿瘤组织中的分级和TIPE2表达是结直肠癌患者总生存期的独立保护因素。此外,构建列线图以预测1年、3年和5年总生存期,并通过校准曲线、受试者工作特征曲线和决策曲线分析曲线进行验证。相关性分析显示,TIPE2和CD8与PD-1和TIM-3呈正相关,表明结直肠癌中TIPE2与T细胞耗竭之间存在潜在联系。TIPE2与肿瘤微环境中CD8、CD20和CD66b等免疫标志物联合可作为结直肠癌患者疾病进展和预后的生物标志物。

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本文引用的文献

1
Prognostic significance of programmed cell death 1 expression on CD8+T cells in various cancers: a systematic review and meta-analysis.程序性细胞死亡蛋白1在各种癌症CD8⁺T细胞上的表达的预后意义:一项系统评价和荟萃分析。
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Immune Infiltration in Tumor and Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes in Early-Stage Lung Cancer.肿瘤及毗邻非肿瘤区域的免疫浸润共同决定早期肺癌患者的临床预后。
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B cells in the tumor microenvironment: Multi-faceted organizers, regulators, and effectors of anti-tumor immunity.
肿瘤微环境中的B细胞:抗肿瘤免疫的多面组织者、调节者和效应器。
Cancer Cell. 2023 Mar 13;41(3):466-489. doi: 10.1016/j.ccell.2023.02.017.
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Knowns and Unknowns about CAR-T Cell Dysfunction.嵌合抗原受体T细胞(CAR-T)功能障碍的已知与未知
Cancers (Basel). 2022 Feb 21;14(4):1078. doi: 10.3390/cancers14041078.
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TIPE2 Promotes Tumor Initiation But Inhibits Tumor Progression in Murine Colitis-Associated Colon Cancer.TIPE2 促进小鼠结肠炎相关结肠癌的肿瘤起始但抑制肿瘤进展。
Inflamm Bowel Dis. 2022 May 4;28(5):764-774. doi: 10.1093/ibd/izab306.
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DNM1: A Prognostic Biomarker Associated with Immune Infiltration in Colon Cancer-A Study Based on TCGA Database.DNM1:与结肠癌免疫浸润相关的预后生物标志物——基于 TCGA 数据库的研究。
Biomed Res Int. 2021 Nov 30;2021:4896106. doi: 10.1155/2021/4896106. eCollection 2021.
7
The overexpression of Tipe2 in CRC cells suppresses survival while endogenous Tipe2 accelerates AOM/DSS induced-tumor initiation.CRC 细胞中 Tipe2 的过表达抑制了存活,而内源性 Tipe2 则加速了 AOM/DSS 诱导的肿瘤起始。
Cell Death Dis. 2021 Oct 26;12(11):1001. doi: 10.1038/s41419-021-04289-0.
8
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Acta Pharm Sin B. 2021 Jun;11(6):1365-1378. doi: 10.1016/j.apsb.2021.03.027. Epub 2021 Apr 24.
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CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.