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整合素β3(ITGB3)作为潜在预后和免疫生物标志物的泛癌分析

Pan-cancer analysis of ITGB3 as a potential prognostic and immunological biomarker.

作者信息

Chen Changshun, Wen Lei, Chen Ge, Yang Fei, Chen Zhong, Ji Jianhua, Gu Jinyi

机构信息

Department of Orthopedics and Trauma Surgery, Affiliated Hospital of Yunnan University, Kunming, 650032, China.

Department of Orthopedics, Nanchong Central Hospital, Nanchong, 637000, China.

出版信息

Discov Oncol. 2025 Apr 12;16(1):522. doi: 10.1007/s12672-025-02300-0.

Abstract

Integrin β3 (ITGB3) acts as a crucial regulator and target within the tumor immune microenvironment (TIME) and is highly expressed in the TIME of various tumors. The TIMER, TCGA, GTEx, and CCLE databases were utilized to comprehensively analyze the differential expression of ITGB3 in tumor tissues. Kaplan-Meier analysis, forest plots, and univariate and multivariate Cox regression were used to assess the genetic alterations, clinicopathological characteristics, and prognostic value of ITGB3. Additionally, the R software package was used to evaluate the relationship between ITGB3 expression and immune cell infiltration, immunomodulatory genes, and immune checkpoints, and potential signaling pathways were examined through differential expression and enrichment analysis. We found that the high expression of ITGB3 is a significant risk factor for six types of cancer, including adrenocortical carcinoma (ACC), and is closely associated with a lower survival rate. Anti-tumor immune cells (CD8 + T cells, CD4 + Th1 cells, and NKT cells) were significantly reduced. By contrast, pro-tumor immune cells (Tregs and CD4 + Th2 cells), immune checkpoints (CTLA4 and PD-CD1), and negatively regulated co-stimulators of T-cell activation (CTLA4, PD-CD1, and IL10) were significantly elevated in most types of cancer with high ITGB3 expression. Overall, our preliminary results indicate that ITGB3 plays an important role in immunosuppression in the tumor microenvironment. Elevated levels of ITGB3 inhibit tumor immunity, facilitate tumor immune escape, and affect patient prognosis, and it may be a prognostic biomarker.

摘要

整合素β3(ITGB3)在肿瘤免疫微环境(TIME)中起着关键的调节作用且是其靶点,在多种肿瘤的TIME中高表达。利用TIMER、TCGA、GTEx和CCLE数据库全面分析ITGB3在肿瘤组织中的差异表达。采用Kaplan-Meier分析、森林图以及单因素和多因素Cox回归来评估ITGB3的基因改变、临床病理特征和预后价值。此外,使用R软件包评估ITGB3表达与免疫细胞浸润、免疫调节基因和免疫检查点之间的关系,并通过差异表达和富集分析检查潜在的信号通路。我们发现ITGB3的高表达是包括肾上腺皮质癌(ACC)在内的六种癌症的显著危险因素,且与较低的生存率密切相关。抗肿瘤免疫细胞(CD8 + T细胞、CD4 + Th1细胞和NKT细胞)显著减少。相比之下,在大多数ITGB3高表达的癌症类型中,促肿瘤免疫细胞(调节性T细胞和CD4 + Th2细胞)、免疫检查点(CTLA4和PD-CD1)以及T细胞活化的负调节共刺激因子(CTLA4、PD-CD1和IL10)显著升高。总体而言,我们的初步结果表明ITGB3在肿瘤微环境的免疫抑制中起重要作用。ITGB3水平升高会抑制肿瘤免疫、促进肿瘤免疫逃逸并影响患者预后,它可能是一种预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/761a/11993531/70b1c1367c42/12672_2025_2300_Fig1_HTML.jpg

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