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突变和11q13扩增是头颈部鳞状细胞癌免疫治疗的潜在预测生物标志物。

Mutation and 11q13 Amplification Are Potential Predictive Biomarkers for Immunotherapy in Head and Neck Squamous Cell Carcinoma.

作者信息

Dou Shengjin, Zhang Lin, Wang Chong, Yao Yanli, Jiang Wen, Ye Lulu, Li Jiang, Wu Sicheng, Sun Debin, Gong Xiaoli, Li Rongrong, Zhu Guopei

机构信息

Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.

Department of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Immunol. 2022 Mar 16;13:813732. doi: 10.3389/fimmu.2022.813732. eCollection 2022.

Abstract

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers. The treatment of HNSCC remains challenging despite recent progress in targeted therapies and immunotherapy. Research on predictive biomarkers in clinical settings is urgently needed.

METHODS

Next-generation sequencing analysis was performed on tumor samples from 121 patients with recurrent or metastatic HNSCC underwent sequencing analysis. Clinicopathological information was collected, and the clinical outcomes were assessed. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and cox regression model was used to conduct multivariate analysis. Fisher's exact tests were used to calculate clinical benefit. A p value of less than 0.05 was designated as significant (p < 0.05).

RESULTS

Chromosome 11q13 amplification (, , , and ) and mutations were significantly associated with decreased PFS and no clinical benefits after treatment with a programmed death 1 (PD-1) inhibitor. The same results were found in the combined positive score (CPS) ≥ 1 subgroup. In patients who were treated with an EGFR antibody instead of a PD-1 inhibitor, a significant difference in PFS and clinical benefits was only observed between patients with CPS ≥ 1 and CPS < 1.

CONCLUSION

Chromosome 11q13 amplification and mutations were negatively correlated with anti-PD-1 therapy. These markers may serve as potential predictive biomarkers to identify patients for whom immunotherapy may be unsuitable.

摘要

背景

头颈部鳞状细胞癌(HNSCC)是最常见的恶性肿瘤之一。尽管靶向治疗和免疫治疗最近取得了进展,但HNSCC的治疗仍然具有挑战性。迫切需要在临床环境中开展预测生物标志物的研究。

方法

对121例复发或转移性HNSCC患者的肿瘤样本进行了二代测序分析。收集临床病理信息并评估临床结局。采用Kaplan-Meier法估计无进展生存期(PFS),并使用cox回归模型进行多因素分析。采用Fisher精确检验计算临床获益。p值小于0.05被定义为具有显著性(p < 0.05)。

结果

11号染色体q13扩增( 、 、 以及 )和 突变与PFS降低以及程序性死亡1(PD-1)抑制剂治疗后无临床获益显著相关。在综合阳性评分(CPS)≥1亚组中也发现了相同的结果。在接受表皮生长因子受体(EGFR)抗体而非PD-1抑制剂治疗的患者中,仅在CPS≥1和CPS<1的患者之间观察到PFS和临床获益的显著差异。

结论

11号染色体q13扩增和 突变与抗PD-1治疗呈负相关。这些标志物可能作为潜在的预测生物标志物,用于识别可能不适合免疫治疗的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601e/8965897/8cca2394d3c9/fimmu-13-813732-g001.jpg

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