Kumari Swati, Mishra Sridhar, Ali Wahid, Singh Uma Shankar, Shabbir Nida, Kumar Vijay, Akhtar Naseem, Hadi Rahat
Department of Pathology, King George Medical University, Lucknow 226003, India.
Department of Plastic & Reconstructive Surgery, King George Medical University, Lucknow 226003, India.
Oral Oncol. 2025 Jun;165:107305. doi: 10.1016/j.oraloncology.2025.107305. Epub 2025 Apr 25.
Over the past decades, significant progress has been made in the early diagnosis and treatment of oropharyngeal squamous cell carcinoma (OPSCC). However, the survival rate has not improved. Human papillomavirus (HPV) is a major risk factor for the development of oropharyngeal cancer. Therefore, understanding the molecular mechanisms underlying OPSCC may help define improved diagnostic and prognostic strategies. Previous studies on tissue samples have linked microRNAs (miRNAs) to the progression of OPSCC. This study aimed to develop a panel of diagnostic biomarkers based on the serum miRNA signature in OPSCC that correlates with HPV status.
Paired serum and tissue samples were collected from 30 OPSCC patients and 20 healthy controls. Based on previous studies on OPSCC tissue samples, a set of six miRNAs (miR-93, miR-222, miR-199, miR-320, miR-145, and miR-126) was selected due to their association with OPSCC development and progression. RT-qPCR was used to compare miRNA expression in paired samples, with miR-16 serving as the reference gene for normalization. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic potential of these serum miRNAs.
The mean relative fold change for serum miR-93 and miR-222 was upregulated, whereas miR-199, miR-320, miR-145, and miR-126 were downregulated in OPSCC compared to normal controls. A similar trend of upregulation and downregulation was observed in tissue samples. The mean relative expression of miR-93 was significantly associated with HPV status (p < 0.0001). Additionally, the mean relative expression levels of all six miRNAs (miR-93, miR-222, miR-199, miR-320, miR-145, and miR-126) were significantly different between the serum of normal controls and early-stage OPSCC patients. The serum miRNA panel, including miR-93, miR-222, miR-199, miR-320, miR-145, and miR-126, demonstrated significant diagnostic potential in distinguishing OPSCC from normal controls.
Our findings suggest that a panel of OPSCC-related miRNAs demonstrates concordant expression levels in serum and tissue of OPSCC, and may serve as a minimally invasive diagnostic biomarker for OPSCC. Further studies with a larger sample size are needed to confirm these findings, particularly in HPV-associated OPSCC.
在过去几十年中，口咽鳞状细胞癌（OPSCC）的早期诊断和治疗取得了显著进展。然而，生存率并未提高。人乳头瘤病毒（HPV）是口咽癌发生的主要危险因素。因此，了解OPSCC的分子机制可能有助于确定改进的诊断和预后策略。先前对组织样本的研究已将微小RNA（miRNA）与OPSCC的进展联系起来。本研究旨在基于与HPV状态相关的OPSCC血清miRNA特征开发一组诊断生物标志物。
从30例OPSCC患者和20例健康对照中收集配对的血清和组织样本。基于先前对OPSCC组织样本的研究，由于其与OPSCC发生和进展的关联，选择了一组六种miRNA（miR-93、miR-222、miR-199、miR-320、miR-145和miR-126）。采用逆转录定量聚合酶链反应（RT-qPCR）比较配对样本中的miRNA表达，以miR-16作为标准化的参考基因。进行受试者工作特征（ROC）曲线分析以评估这些血清miRNA的诊断潜力。
与正常对照相比，OPSCC患者血清中miR-93和miR-222的平均相对倍数变化上调，而miR-199、miR-320、miR-145和miR-126下调。在组织样本中观察到类似的上调和下调趋势。miR-93的平均相对表达与HPV状态显著相关（p < 0.0001）。此外，正常对照血清与早期OPSCC患者血清中所有六种miRNA（miR-93、miR-222、miR-199、miR-320、miR-145和miR-126）的平均相对表达水平存在显著差异。包括miR-93、miR-222、miR-199、miR-320、miR-145和miR-126的血清miRNA组在区分OPSCC与正常对照方面显示出显著的诊断潜力。
我们的研究结果表明，一组与OPSCC相关的miRNA在OPSCC的血清和组织中表现出一致的表达水平，并且可能作为OPSCC的微创诊断生物标志物。需要进行更大样本量的进一步研究来证实这些发现，特别是在HPV相关的OPSCC中。
