帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Construction and validation of an anoikis-related long non-coding RNA-based prognostic model for head and neck squamous cell carcinoma.
Construction and validation of an anoikis-related long non-coding RNA-based prognostic model for head and neck squamous cell carcinoma.
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我们成功建立了一个基于 ARLncs 的新型预后模型,该模型在预测 HNSCC 患者的预后和个性化治疗方面具有重要前景。
作为一种独特的细胞凋亡形式,失巢凋亡显著影响肿瘤生物学。研究已揭示长链非编码RNA(lncRNA)在癌症信号通路中的多样作用;然而,失巢凋亡相关长链非编码RNA(ARLncs)在头颈部鳞状细胞癌(HNSCC)中的预后意义尚未被探索。因此,本研究旨在建立风险模型并评估其对HNSCC个体预后和免疫景观的预测能力。
从癌症基因组图谱(TCGA)中检索了HNSCC的数据。从GeneCards获取了失巢凋亡相关基因,随后通过Pearson相关分析识别了ARLxncs。从TCGA的HNSCC样本中共提取了268个ARLncs,并使用Pearson分析识别了高度相关的ARLncs。对这些ARLncs进行了全面的生物信息学分析,包括单因素Cox回归和最小绝对收缩和选择算子分析,并生成了总生存期(OS)评分和OS特征。
基于风险评分,将HNSCC患者分为高风险和低风险亚组,以评估通路富集、预后、免疫浸润水平、肿瘤突变负荷和药物敏感性方面的差异。TCGA-HNSCC样本被分为两个亚型(聚类1和聚类2),其中聚类2的患者比聚类1的患者表现出更差的预后和更高水平的TIL(肿瘤浸润淋巴细胞)(TILs)。随后,我们构建了一个有效的HNSCC中12个ARLncs的预后风险模型,该模型在预测预后方面表现出有效性。高风险评分患者比低风险评分患者表现出显著更差的OS、更低的TILs数量和更低的化疗药物敏感性。
As a unique form of apoptosis, anoikis significantly influences tumor biology. Studies have revealed the diverse roles of long non-coding RNAs (lncRNAs) in cancer signaling pathways; however, the prognostic significance of anoikis-related long non-coding RNAs (ARLncs) in head and neck squamous cell carcinoma (HNSCC) remains unexplored. Therefore, this research was undertaken to establish a risk model and assess its predictive ability for prognosis and immune landscape in individuals with HNSCC.
Data on HNSCC were retrieved from The Cancer Genome Atlas (TCGA). Anoikis-associated genes were acquired from GeneCards, followed by identification of ARLxncs using Pearson correlation analysis. A total of 268 ARLncs from HNSCC samples were extracted from TCGA, and highly relevant ARLncs were identified using Pearson analysis. These ARLncs were subjected to comprehensive bioinformatics analyses, including univariate Cox regression and least absolute shrinkage and selection operator analyses, and an overall survival (OS)-score and OS-signature were generated.
Based on the risk score, patients with HNSCC were stratified into high- and low-risk subgroups to assess the differences in pathway enrichment, prognosis, immune infiltration level, tumor mutation burden, and drug susceptibility. TCGA-HNSCC samples were divided into two subtypes (clusters 1 and 2), with patients in cluster 2 exhibiting worse prognosis and higher levels of tumor-infiltrating lymphocytes (TILs) than patients in cluster 1. Subsequently, we constructed a valid prognostic risk model comprising 12 ARLncs in HNSCC that demonstrated efficacy in predicting prognosis. Patients with high-risk scores exhibited significantly worse OS, lower numbers of TILs, and lower sensitivity to chemotherapy drugs than patients with low-risk scores.
Overall, we successfully established a novel prognostic model based on ARLncs, which holds significant promise for predicting prognosis and personalized therapy for patients with HNSCC.
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