Saidak Zuzana, Milly Marie, Louandre Christophe, Colin Emilien, Rusu Pia-Manuela, Paasche Agnes, Dakpe Stephanie, Testelin Sylvie, Galmiche Antoine
UR7516, CHIMERE, Université de Picardie Jules Verne, Amiens, France.
Service de Biochimie, Centre de Biologie Humaine, CHU Amiens, Amiens, France.
Front Oral Health. 2025 Jun 11;6:1614371. doi: 10.3389/froh.2025.1614371. eCollection 2025.
Non-invasive analysis of tumor DNA in biological fluids offers promising perspectives for the oncological monitoring of cancer patients. Cancer-specific DNA methylation marks are detectable in the saliva of Oral Squamous Cell Carcinoma (OSCC) patients. We set up a salivary liquid biopsy approach for the oncological monitoring of OSCC referred for surgical resection.
We analysed DNA methylation in TCGA-OSCC to identify genes with high methylation levels in tumor vs. matched non-tumor tissue. Cell-free DNA (cfDNA) methylation levels of selected genes were analysed in the saliva of OSCC patients ( = 30) before/after complete surgical resection by High Resolution Melting (HRM) analysis, and compared to non-cancer controls.
We identified five genes with higher DNA methylation levels in OSCC compared to matching non-tumor tissue that were analysable by HRM, and were independent of tumor stage, etiology or age. In 70% of OSCC, at least one of the five cfDNA methylation marks was detectable before surgery. Complete surgical resection led to a significant disappearance of salivary cfDNA methylation marks. In 52% of patients, we noted the persistence of at least one mark, shown to be related to close/positive surgical margin status. In one patient resected with R0 margin, the persistence of methylation preceded tumor recurrence by 4 months.
Salivary cfDNA methylation analysis offers a minimally invasive method to monitor the effectiveness of surgical resection of OSCC. Future studies with a larger cohort and longer follow-up are required to validate its use in this context.
对生物体液中的肿瘤DNA进行无创分析，为癌症患者的肿瘤学监测提供了广阔前景。口腔鳞状细胞癌（OSCC）患者的唾液中可检测到癌症特异性DNA甲基化标记。我们建立了一种唾液液体活检方法，用于对接受手术切除的OSCC患者进行肿瘤学监测。
我们分析了TCGA-OSCC中的DNA甲基化，以确定肿瘤组织与匹配的非肿瘤组织中甲基化水平较高的基因。通过高分辨率熔解（HRM）分析，对30例OSCC患者手术完全切除前后唾液中所选基因的游离DNA（cfDNA）甲基化水平进行分析，并与非癌症对照进行比较。
我们鉴定出5个基因，与匹配的非肿瘤组织相比，OSCC中的DNA甲基化水平更高，这些基因可通过HRM进行分析，且与肿瘤分期、病因或年龄无关。在70%的OSCC患者中，术前可检测到5个cfDNA甲基化标记中的至少一个。手术完全切除导致唾液cfDNA甲基化标记显著消失。在52%的患者中，我们注意到至少一个标记持续存在，这与手术切缘接近/阳性状态有关。在一名切缘为R0的患者中，甲基化持续存在比肿瘤复发早4个月。
唾液cfDNA甲基化分析提供了一种微创方法来监测OSCC手术切除的效果。需要进行更大样本量和更长随访时间的未来研究，以验证其在这种情况下的应用。
