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基于转化生长因子信号通路的模型预测头颈部鳞状细胞癌的亚型和预后

TGF- Signaling Pathway-Based Model to Predict the Subtype and Prognosis of Head and Neck Squamous Cell Carcinoma.

作者信息

Zheng Lian, Guan Zhenjie, Xue Miaomiao

机构信息

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Genet. 2022 May 2;13:862860. doi: 10.3389/fgene.2022.862860. eCollection 2022.

Abstract

Although immunotherapy with immune checkpoint therapy has been used to treat head and neck squamous cell carcinoma (HNSCC), response rates and treatment sensitivity remain limited. Recent studies have indicated that transforming growth factor-β (TGF-β) may be an important target for novel cancer immunotherapies. We collected genomic profile data from The Cancer Genome Atlas and Gene Expression Omnibus. The least absolute shrinkage and selection operator method and Cox regression were used to establish a prognostic model. Gene set enrichment analysis was applied to explore biological functions. Tracking of indels by decomposition and subclass mapping algorithms were adopted to evaluate immunotherapy efficiency. We established a seven TGF-β pathway-associated gene signature with good prediction efficiency. The high-risk score subgroup mainly showed enrichment in tumor-associated signaling such as hypoxia and epithelial-mesenchymal transition (EMT) pathways; This subgroup was also associated with tumor progression. The low-risk score subgroup was more sensitive to immunotherapy and the high-risk score subgroup to cisplatin, erlotinib, paclitaxel, and crizotinib. The TGF- pathway signature gene model provides a novel perspective for evaluating effectiveness pre-immunotherapy and may guide further studies of precision immuno-oncology.

摘要

尽管免疫检查点疗法的免疫疗法已被用于治疗头颈部鳞状细胞癌(HNSCC),但其缓解率和治疗敏感性仍然有限。最近的研究表明,转化生长因子-β(TGF-β)可能是新型癌症免疫疗法的一个重要靶点。我们从癌症基因组图谱和基因表达综合数据库收集了基因组概况数据。使用最小绝对收缩和选择算子方法及Cox回归建立了一个预后模型。应用基因集富集分析来探索生物学功能。采用通过分解和亚类映射算法追踪插入缺失来评估免疫疗法的效率。我们建立了一个具有良好预测效率的7个TGF-β通路相关基因特征。高风险评分亚组主要在缺氧和上皮-间质转化(EMT)通路等肿瘤相关信号中表现出富集;该亚组也与肿瘤进展相关。低风险评分亚组对免疫疗法更敏感,而高风险评分亚组对顺铂、厄洛替尼、紫杉醇和克唑替尼更敏感。TGF-通路特征基因模型为免疫治疗前评估疗效提供了新的视角,并可能指导精准免疫肿瘤学的进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ce/9108263/b5cda5349984/fgene-13-862860-g001.jpg

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