PDF(Pubmed)
Abstract：
UNASSIGNED: Head and neck squamous cell carcinoma (HNSCC) is an epithelial malignant tumor originating from the oral cavity, oropharynx, nasal cavity, sinuses, nasopharynx, hypopharynx, or larynx. Mutations in TP53 are the most common of all somatic genomic changes in HNSCC, and TP53 mutations are associated with the response to immunotherapy and chemotherapy. Tumor-derived circulating cell-free DNA (cfDNA) is a minimally invasive method to determining genetic alterations in cancer. This study aimed to explore the therapeutic responses of patients with HNSCC with TP53 mutation and the accuracy of cfDNA for detecting TP53 mutation.
UNASSIGNED: Information on TP53 mutations, patient survival time, and clinical data in HNSCC were downloaded from The Cancer Genome Atlas database. The difference in immune infiltration between the TP53-mutant group and the wild-type group was compared. We applied the single-sample gene set enrichment analysis method on the transcriptome of HNSCC samples to assess the distribution of immune cell types between the two groups. The chemotherapy response was constructed using the R software package, \"pRRophetic\". Gene set enrichment analysis was performed based on the TP53 mutation. The next-generation sequencing was executed on cfDNA from nine patients with HNSCC to detect genetic alterations. Tumor biopsy (n=9) was sequenced using the same technique.
UNASSIGNED: TP53 was the most frequently mutated gene in HNSCC. The TP53 mutation was related to immune cells and the expression of immune-associated genes. The TP53 mutation group showed lower response to immunotherapy but high sensitivity to some chemotherapies compared with the wild-type group. TP53 was the most frequently mutated gene (6/9; 66.67%) in cfDNA. Only 27.27% of TP53 mutations in tumor tissue were detected outside of cfDNA.
UNASSIGNED: TP53 mutation could be used as a specific predictor of treatment response in patients with HNSCC. Using cfDNA to detect the TP53 mutations in patients with HSNCC is a feasible method. The results suggested that the therapeutic response in patients could be predicted by detecting TP53 mutations in cfDNA, and large-scale and prospective studies are needed to validate this hypothesis.
UNASSIGNED: Information on TP53 mutations, patient survival time, and clinical data in HNSCC were downloaded from The Cancer Genome Atlas database. The difference in immune infiltration between the TP53-mutant group and the wild-type group was compared. We applied the single-sample gene set enrichment analysis method on the transcriptome of HNSCC samples to assess the distribution of immune cell types between the two groups. The chemotherapy response was constructed using the R software package, \"pRRophetic\". Gene set enrichment analysis was performed based on the TP53 mutation. The next-generation sequencing was executed on cfDNA from nine patients with HNSCC to detect genetic alterations. Tumor biopsy (n=9) was sequenced using the same technique.
UNASSIGNED: TP53 was the most frequently mutated gene in HNSCC. The TP53 mutation was related to immune cells and the expression of immune-associated genes. The TP53 mutation group showed lower response to immunotherapy but high sensitivity to some chemotherapies compared with the wild-type group. TP53 was the most frequently mutated gene (6/9; 66.67%) in cfDNA. Only 27.27% of TP53 mutations in tumor tissue were detected outside of cfDNA.
UNASSIGNED: TP53 mutation could be used as a specific predictor of treatment response in patients with HNSCC. Using cfDNA to detect the TP53 mutations in patients with HSNCC is a feasible method. The results suggested that the therapeutic response in patients could be predicted by detecting TP53 mutations in cfDNA, and large-scale and prospective studies are needed to validate this hypothesis.
摘要：
■头颈部鳞状细胞癌（HNSCC）是一种起源于口腔的上皮恶性肿瘤，口咽,鼻腔,鼻窦,鼻咽部,下咽,或者喉部.TP53突变是HNSCC所有体细胞基因组变化中最常见的，TP53突变与免疫治疗和化疗的反应相关。肿瘤来源的循环无细胞DNA（cfDNA）是一种确定癌症遗传改变的微创方法。本研究旨在探讨TP53突变的HNSCC患者的治疗反应以及cfDNA检测TP53突变的准确性。
■有关TP53突变的信息，患者生存时间,从癌症基因组图谱数据库下载HNSCC的临床数据。比较TP53突变体组与野生型组之间的免疫浸润差异。我们将单样本基因集富集分析方法应用于HNSCC样本的转录组，以评估两组之间的免疫细胞类型分布。使用R软件包构建化疗反应，\"pRophetic\"。基于TP53突变进行基因集富集分析。对9名HNSCC患者的cfDNA进行了下一代测序，以检测遗传改变。使用相同技术对肿瘤活检(n=9)进行测序。
■TP53是HNSCC中最常见的突变基因。TP53突变与免疫细胞和免疫相关基因的表达有关。与野生型组相比，TP53突变组对免疫疗法的反应较低，但对某些化学疗法的敏感性较高。TP53是cfDNA中最常见的突变基因(6/9;66.67%)。在cfDNA之外检测到肿瘤组织中仅27.27%的TP53突变。
■TP53突变可作为HNSCC患者治疗反应的特异性预测因子。使用cfDNA检测HSNCC患者的TP53突变是一种可行的方法。结果表明，可以通过检测cfDNA中的TP53突变来预测患者的治疗反应，需要大规模和前瞻性研究来验证这一假设。
■有关TP53突变的信息，患者生存时间,从癌症基因组图谱数据库下载HNSCC的临床数据。比较TP53突变体组与野生型组之间的免疫浸润差异。我们将单样本基因集富集分析方法应用于HNSCC样本的转录组，以评估两组之间的免疫细胞类型分布。使用R软件包构建化疗反应，\"pRophetic\"。基于TP53突变进行基因集富集分析。对9名HNSCC患者的cfDNA进行了下一代测序，以检测遗传改变。使用相同技术对肿瘤活检(n=9)进行测序。
■TP53是HNSCC中最常见的突变基因。TP53突变与免疫细胞和免疫相关基因的表达有关。与野生型组相比，TP53突变组对免疫疗法的反应较低，但对某些化学疗法的敏感性较高。TP53是cfDNA中最常见的突变基因(6/9;66.67%)。在cfDNA之外检测到肿瘤组织中仅27.27%的TP53突变。
■TP53突变可作为HNSCC患者治疗反应的特异性预测因子。使用cfDNA检测HSNCC患者的TP53突变是一种可行的方法。结果表明，可以通过检测cfDNA中的TP53突变来预测患者的治疗反应，需要大规模和前瞻性研究来验证这一假设。
