Dal Secco Chiara, Tel Alessandro, Allegri Lorenzo, Baldan Federica, Curcio Francesco, Sembronio Salvatore, Faletra Flavio, Robiony Massimo, Damante Giuseppe, Mio Catia
Department of Medicine (DMED), University of Udine, Udine, Italy.
Clinic of Maxillofacial Surgery, Head-Neck and NeuroScience Department, University Hospital of Udine, Udine, Italy.
Front Oncol. 2024 Nov 1;14:1480302. doi: 10.3389/fonc.2024.1480302. eCollection 2024.
Liquid biopsy is gaining momentum for diagnosis and surveillance of cancer patients. Indeed, head and neck squamous cell carcinoma (HNSCC) is burdened with poor prognosis and high recurrence rates after treatment. It is therefore crucial to be able to detect minimal residual disease early after radical treatment or relapse, so surgery can be performed when the disease is still resectable. In this scenario, aim of this study is to create a liquid biopsy-based pipeline able to detect somatic tumor mutations in a cohort of HNSCC-affected patients undergoing follow-up after surgical intervention.
Our cohort included 17 patients diagnosed with HNSCC over 4 years. The first saliva sample was collected before surgery while the rest were collected during the subsequent visits, according to the follow-up schedule. Salivary DNA (sDNA) was extracted, and a 52-gene next generation sequencing (NGS)-based panel was used for somatic variants detection.
41.2% of samples collected before surgery bore a deleterious variant (n=7/17). Overall, 29.2% of samples harbored at least a pathogenic variant (n=21/72). The most frequently mutated genes were TP53 (80%), FBXW7 (8%), PDGFRA (4%) and PTEN (4%). Finally, three patients experienced a loco-regional relapse by clinical evaluations, anticipated in 67% of cases by the molecular one (n=2/3).
Our data indicate that sDNA could aid in the monitoring of patients' follow-up as low-frequency somatic mutations could be assessed from the saliva of HNSCC patients. Prospectively, these results suggest that salivary-based liquid biopsy might pave the way for personalized molecular therapies based on mutational data.
液体活检在癌症患者的诊断和监测方面正日益受到关注。事实上，头颈部鳞状细胞癌（HNSCC）预后较差，治疗后复发率高。因此，在根治性治疗或复发后早期检测到微小残留疾病至关重要，这样在疾病仍可切除时就能进行手术。在这种情况下，本研究的目的是创建一个基于液体活检的流程，能够在一组接受手术干预后进行随访的HNSCC患者队列中检测体细胞肿瘤突变。
我们的队列包括4年内被诊断为HNSCC的17名患者。第一份唾液样本在手术前采集，其余样本根据随访计划在随后的就诊时采集。提取唾液DNA（sDNA），并使用基于52基因下一代测序（NGS）的检测板来检测体细胞变异。
手术前采集的样本中有41.2%携带有害变异（n = 7/17）。总体而言，29.2%的样本至少携带一种致病变异（n = 21/72）。最常发生突变的基因是TP53（80%）、FBXW7（8%）、PDGFRA（4%）和PTEN（4%）。最后，三名患者经临床评估出现局部区域复发，其中67%的病例在分子检测中提前检测到（n = 2/3）。
我们的数据表明，sDNA有助于监测患者的随访情况，因为可以从HNSCC患者的唾液中评估低频体细胞突变。前瞻性地看，这些结果表明基于唾液的液体活检可能为基于突变数据的个性化分子治疗铺平道路。
