Area Medicina Oral Departamento de Patología Facultad de Odontología, Universidad de Chile, Av. Olivos 243, Independencia, Región Metropolitana, CP8320000, Santiago, Chile.
Instituto Nacional del Cáncer, Av. Profesor Zañartu 1010, Independencia, Región Metropolitana, CP8320000, Santiago, Chile.
Sci Rep. 2021 Mar 25;11(1):6939. doi: 10.1038/s41598-021-86208-z.
The oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide. Changes in SPINK7 in precancerous lesions could promote oncogenesis. Our aim was to evaluate SPINK7 as a potential molecular biomarker which predicts OSCC stages, compared to: HER2, TP53, RB1, NFKB and CYP4B1. This study used oral biopsies from three patient groups: dysplasia (n = 33), less invasive (n = 28) and highly invasive OSCC (n = 18). The control group consisted of clinically suspicious cases later to be confirmed as normal mucosa (n = 20). Gene levels of SPINK7, P53, RB, NFKB and CYP4B1 were quantified by qPCR. SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also, SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal-Wallis test and Dunn's post-hoc with a p < 0.05 significance was used to analyze data. In OSCC, the SPINK7 expression had down regulated while P53, RB, NFKB and CYP4B1 had up regulated (p < 0.001). SPINK7 had also diminished in TCGA patients (p = 2.10e-6). In less invasive OSCC, SPINK7 and HER2 proteins had decreased while TP53 and RB1 had increased with respect to the other groups (p < 0.05). The changes of SPINK7 accompanied by HER2, P53 and RB1 can be used to classify the molecular stage of OSCC lesions allowing a diagnosis at molecular and histopathological levels.
口腔鳞状细胞癌（OSCC）发病率高，影响全球患者。癌前病变中 SPINK7 的变化可能促进肿瘤发生。我们的目的是评估 SPINK7 作为一种潜在的分子生物标志物，与 HER2、TP53、RB1、NFKB 和 CYP4B1 相比，预测 OSCC 分期。本研究使用来自三组患者的口腔活检样本：发育不良（n=33）、侵袭性较低（n=28）和高度侵袭性 OSCC（n=18）。对照组由后来被证实为正常粘膜的临床可疑病例组成（n=20）。通过 qPCR 定量 SPINK7、P53、RB、NFKB 和 CYP4B1 的基因水平。还通过免疫荧光法评估了 SPINK7、HER2、TP53 和 RB1。使用单向 Kruskal-Wallis 检验和 Dunn 事后检验，p<0.05 为显著性差异。在 OSCC 中，SPINK7 表达下调，而 P53、RB、NFKB 和 CYP4B1 表达上调（p<0.001）。在 TCGA 患者中，SPINK7 也减少了（p=2.10e-6）。在侵袭性较低的 OSCC 中，与其他组相比，SPINK7 和 HER2 蛋白减少，而 TP53 和 RB1 蛋白增加（p<0.05）。SPINK7 的变化伴随着 HER2、P53 和 RB1 的变化，可以用于对 OSCC 病变的分子阶段进行分类，从而在分子和组织病理学水平上进行诊断。
