Baiju Denis C, Ravi Joshua, Sarma Mridul, Sureshan Muthusamy, Jothi Arunachalam, Mondal Rosy
School of Chemical and Biotechnology, SASTRA Deemed University, Thirumalaisamudram, Trichy-Tanjore Road, Tamil Nadu 613401, India.
200 Bedded Cancer Hospital, GMCH Top Hill Road, Indrapur, Guwahati, Assam 781034, India.
Oral Oncol. 2025 Jul;166:107387. doi: 10.1016/j.oraloncology.2025.107387. Epub 2025 May 28.
Oral Squamous Cell Carcinoma (OSCC) is the most commonly diagnosed cancer worldwide, with 90-95% of cases reported to be SCC. The present study aimed to investigate the presence of circulating cell-free tumor DNA (cftDNA) in the patient's plasma with OSCC and determine the feasibility of liquid biopsies in genomic profiling using deep sequencing-based approach. Mutation analysis of cfDNA will help evaluate the molecular and clinical impacts of the identified somatic alterations during primary staging.
Paired samples from 11 OSCC patients, including cfDNA, tumor tissue, and blood, were submitted for deep sequencing of 50 genes by next-generation sequencing using the Ion Ampliseq Cancer Hotspot Panel v2.
We found higher mutational load in cfDNA than in tumor tissue samples, suggesting the potential of cfDNA as a liquid biopsy for monitoring therapeutic responses. The TP53 p.Pro72Arg variant was identified in all the samples, indicating its potential as a diagnostic marker. Molecular dynamics simulations of the p53 protein showed higher fluctuations in the mutant form, potentially affecting protein function. The RB1 p.Ile680Thr pathogenic variant was found in 64% of oral squamous cell carcinoma samples. Recurrently mutated genes, including TP53, KDR, APC, RB1, MET, PIK3CA, CDKN2A, RET, and EGFR, were identified in both tumor tissue and cfDNA samples.
The detection of tumor imprints and heterogeneity in cfDNA samples highlights the potential of liquid biopsy as a valuable tool for monitoring therapeutic responses in OSCC. The identification of recurrently mutated genes and pathogenic variants provides insights into potential therapeutic targets.
口腔鳞状细胞癌（OSCC）是全球诊断最常见的癌症，据报道90 - 95%的病例为鳞状细胞癌（SCC）。本研究旨在调查OSCC患者血浆中循环游离肿瘤DNA（cftDNA）的存在情况，并确定使用基于深度测序的方法进行液体活检在基因组分析中的可行性。cfDNA的突变分析将有助于评估在初次分期期间所识别的体细胞改变的分子和临床影响。
来自11例OSCC患者的配对样本，包括cfDNA、肿瘤组织和血液，使用Ion Ampliseq Cancer Hotspot Panel v2通过下一代测序提交用于50个基因的深度测序。
我们发现cfDNA中的突变负荷高于肿瘤组织样本，表明cfDNA作为监测治疗反应的液体活检的潜力。在所有样本中均鉴定出TP53 p.Pro72Arg变体，表明其作为诊断标志物的潜力。p53蛋白的分子动力学模拟显示突变形式具有更高的波动，可能影响蛋白质功能。在64%的口腔鳞状细胞癌样本中发现了RB1 p.Ile680Thr致病变体。在肿瘤组织和cfDNA样本中均鉴定出包括TP53、KDR、APC、RB1、MET、PIK3CA、CDKN2A、RET和EGFR在内的复发性突变基因。
cfDNA样本中肿瘤印记和异质性的检测突出了液体活检作为监测OSCC治疗反应的有价值工具的潜力。复发性突变基因和致病变体的鉴定为潜在治疗靶点提供了见解。
