University of Coimbra, Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, Coimbra, Portugal.
University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra, Portugal.
Oncogene. 2021 Jun;40(22):3859-3869. doi: 10.1038/s41388-021-01806-5. Epub 2021 May 10.
The prognosis of oral squamous cell carcinoma (OSCC) patients remains poor without implemented biomarkers in the clinical routine practice to help in the patient's management. With this study we aimed to identify specific prognostic biomarkers for OSCC using a whole genome technology as well as to verify the clinical utility of a head and neck cancer-specific multiplex ligation-dependent probe amplification (MLPA) panel. A genomic characterization of tumor samples from 62 OSCC patients was performed using array comparative genomic hybridization (aCGH) and a more straightforward and cost-effective molecular technology, MLPA. The identification of a genomic signature and prognosis biomarkers was carried out by applying several statistical methods. With aCGH we observed that the chromosomes most commonly altered were 3p, 3q, 5q, 6p, 7q, 8p, 8q, 11q, 15q, 17q, and 18q. The MLPA results showed that the chromosomes with a higher frequency of alterations were 3p, 3q, 8p, 8q, and 11q. We identified a genomic signature with seven genes OCLN (3p21.31), CLDN16 (3q29), SCRIB (3q29), IKBKB (3q22.3), PAK2 (8q22.3), PIK3CB (3q28), and YWHAZ (8q24.3) that together allow to differentiate the patients that developed metastases or relapses after primary tumor treatment, with an overall accuracy of 79%. Amplification of PIK3CB as a predictor of metastases or relapses development was validated using TCGA data. This amplified gene showed a reduction in more than 5 years in the median survival of the patients. The identified biomarkers might have a significant impact in the patients' management and could leverage the OSCC precision medicine.
口腔鳞状细胞癌(OSCC)患者的预后仍然较差,临床常规实践中没有实施的生物标志物来帮助患者管理。本研究旨在使用全基因组技术鉴定 OSCC 的特定预后生物标志物,并验证头颈癌特异性多重连接依赖性探针扩增(MLPA)试剂盒的临床实用性。使用 array comparative genomic hybridization (aCGH) 和更简单、更具成本效益的分子技术 MLPA 对 62 名 OSCC 患者的肿瘤样本进行了基因组特征分析。通过应用几种统计方法来确定基因组特征和预后生物标志物。通过 aCGH 我们观察到最常改变的染色体是 3p、3q、5q、6p、7q、8p、8q、11q、15q、17q 和 18q。MLPA 结果显示,改变频率较高的染色体是 3p、3q、8p、8q 和 11q。我们鉴定了一个包含七个基因的基因组特征:OCLN(3p21.31)、CLDN16(3q29)、SCRIB(3q29)、IKBKB(3q22.3)、PAK2(8q22.3)、PIK3CB(3q28)和 YWHAZ(8q24.3),它们共同可以区分原发性肿瘤治疗后发生转移或复发的患者,总体准确率为 79%。使用 TCGA 数据验证了 PIK3CB 的扩增作为转移或复发发展的预测因子。这种扩增基因导致患者的中位生存期缩短了 5 年以上。鉴定的生物标志物可能对患者的管理产生重大影响,并可以推动 OSCC 的精准医学。