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鉴定细胞粘附相关亚型并构建风险模型以预测乳腺癌的预后和免疫特性。

Identification of cell adhesion-related subtypes and construction of risk model to predict breast cancer prognostic and immunological properties.

作者信息

Lv De-Ming, Yang Li, Fan Chen, Fang Ling-Hui, Cheng Su-Fen

机构信息

Department of Breast Thyroid Surgery, Jinhua Maternal And Child Health Care Hospital, Jinhua, 321000, China.

出版信息

World J Surg Oncol. 2025 Apr 22;23(1):152. doi: 10.1186/s12957-025-03802-5.

Abstract

BACKGROUND

Breast invasive carcinoma is the most common form of breast cancer, often resulting in recurrence or metastasis in patients. Cell adhesion molecules play a crucial role in modulating the interactions between tumor cells and surrounding cells. The study aims to identify breast cancer subtypes related to cell adhesion and develop prognostic models that are essential for evaluating the prognostic risk and immunological profile of breast cancer.

METHODS

Transcriptome and clinical data were obtained from The Cancer Genome Atlas (TCGA) database, while cell adhesion-related genes (CARGs) from the MSigDB database. Molecular subtyping was performed using NMF clustering. Cox regression and Least absolute shrinkage and selection operator (LASSO) regression analyses were employed to construct a risk model for predicting patient prognosis. This model was validated in independent Gene Expression Omnibus (GEO) datasets, specifically GSE20685 and GSE42568. Immune cell infiltration was explored utilizing the CIBERSORT algorithm. Subsequently, we analyzed tumor mutation burden (TMB). Finally, potential drugs and drug sensitivity was evaluated using pRRobhetic algorithm.

RESULTS

Based on the expression levels of 39 genes related to cell adhesion, we identified 3 distinct subtypes, and LASSO regression analysis identified 8 genes that could be used as prognostic markers. Receiver operating characteristic (ROC) curves demonstrated that these cell adhesion genes were effective in predicting patient prognosis. Compared to the high-risk group, the low-risk group had a more favorable prognosis and a greater response to immunotherapy. These prognostic genes were found to be closely associated with immune cell infiltration and the response to immunotherapy. Furthermore, their significant associations with breast cancer sensitivities to anti-cancer drugs were revealed.

CONCLUSION

We developed a risk model focused on cell adhesion-related genes. This model accurately predicts the prognosis for breast cancer patients. It may also offer new insights for clinical decisions and immunotherapy.

摘要

背景

乳腺浸润性癌是乳腺癌最常见的形式,常导致患者复发或转移。细胞黏附分子在调节肿瘤细胞与周围细胞之间的相互作用中起关键作用。本研究旨在识别与细胞黏附相关的乳腺癌亚型,并开发对评估乳腺癌预后风险和免疫特征至关重要的预后模型。

方法

从癌症基因组图谱(TCGA)数据库获取转录组和临床数据,同时从MSigDB数据库获取细胞黏附相关基因(CARGs)。使用非负矩阵分解(NMF)聚类进行分子亚型分类。采用Cox回归和最小绝对收缩和选择算子(LASSO)回归分析构建预测患者预后的风险模型。该模型在独立的基因表达综合数据库(GEO)数据集,即GSE20685和GSE42568中进行了验证。利用CIBERSORT算法探索免疫细胞浸润情况。随后,我们分析了肿瘤突变负担(TMB)。最后,使用pRRobhetic算法评估潜在药物和药物敏感性。

结果

基于39个与细胞黏附相关基因的表达水平,我们识别出3种不同的亚型,LASSO回归分析确定了8个可作为预后标志物的基因。受试者工作特征(ROC)曲线表明,这些细胞黏附基因在预测患者预后方面是有效的。与高危组相比,低危组预后更好,对免疫治疗的反应更强。发现这些预后基因与免疫细胞浸润和免疫治疗反应密切相关。此外,还揭示了它们与乳腺癌对抗癌药物敏感性的显著关联。

结论

我们开发了一个聚焦于细胞黏附相关基因的风险模型。该模型准确预测了乳腺癌患者的预后。它还可能为临床决策和免疫治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fae/12013005/095e8145c4bb/12957_2025_3802_Fig1_HTML.jpg

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