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成纤维细胞生长因子受体 3 与突变型 p53 的共表达及其与口咽鳞状细胞癌不良预后的关系。

Co-expression of fibroblast growth factor receptor 3 with mutant p53, and its association with worse outcome in oropharyngeal squamous cell carcinoma.

机构信息

Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, Georgia, United States of America.

Department of Pathology, Cleveland Clinic, Cleveland, Ohio, United States of America.

出版信息

PLoS One. 2021 Feb 24;16(2):e0247498. doi: 10.1371/journal.pone.0247498. eCollection 2021.

Abstract

Fibroblast growth factor receptor 3 (FGFR3) is expressed in squamous cell carcinoma of the head and neck (SCCHN) including oropharyngeal squamous cell carcinoma (OPSCC) and is a potential therapeutic target. However, information on its correlation with other relevant cancer related proteins stratified by p16 status and its prognostic significance in OPSCC is limited. We examined FGFR3 expression and its correlation with clinical characteristics, p16 status, and mutant p53 (mp53) among 220 retrospectively collected OPSCC cases and 40 prospectively collected SCCHN cases, including a majority of OPSCC. Correlations of FGFR3 Weighted Index (WI) with p16 status and mp53 WI as well as its association with disease-free survival (DFS) and overall survival (OS) were evaluated. FGFR3 expression was detected in 61% and 70% of cases in cohorts 1 and 2, respectively. FGFR3 level was significantly higher in p16-negative tumors in both cohorts (p<0.001 and 0.006). FGFR3 expression was highly correlated with mp53 expression in both p16 + and p16- OPSCC (p<0.0001 and p = 0.0006, respectively). In cohort 1, univariate analysis showed that FGFR3 was associated with DFS but not OS. Kaplan-Meier analysis showed that higher FGFR3 and mp53 level correlated with worse DFS (p = 0.025) and OS (p = 0.009). As expected, p16 positive status was associated with improved OS and DFS (p<0.001 for both). Our results suggest that high FGFR3 expression is associated with p16 negative status and mp53 expression in OPSCC and correlates with a worse clinical outcome. The biological relationship between FGFR3 and mp53 in OPSCC deserves further investigation.

摘要

成纤维细胞生长因子受体 3(FGFR3)在头颈部鳞状细胞癌(SCCHN)中表达,包括口咽鳞状细胞癌(OPSCC),是一个潜在的治疗靶点。然而,关于其与其他相关癌症相关蛋白的相关性,以及在 OPSCC 中的预后意义,在 p16 状态分层方面的信息有限。我们检测了 220 例回顾性收集的 OPSCC 病例和 40 例前瞻性收集的 SCCHN 病例中 FGFR3 的表达及其与临床特征、p16 状态和突变型 p53(mp53)的相关性,其中包括大多数 OPSCC。评估了 FGFR3 加权指数(WI)与 p16 状态和 mp53 WI 的相关性,以及与无病生存率(DFS)和总生存率(OS)的关系。在队列 1 和队列 2 中,分别有 61%和 70%的病例检测到 FGFR3 表达。在两个队列中,p16 阴性肿瘤的 FGFR3 水平均显著升高(p<0.001 和 0.006)。在 p16+和 p16- OPSCC 中,FGFR3 表达与 mp53 表达高度相关(p<0.0001 和 p=0.0006)。在队列 1 中,单因素分析显示 FGFR3 与 DFS 相关,但与 OS 无关。Kaplan-Meier 分析显示,较高的 FGFR3 和 mp53 水平与较差的 DFS(p=0.025)和 OS(p=0.009)相关。正如预期的那样,p16 阳性状态与改善的 OS 和 DFS 相关(两者均为 p<0.001)。我们的结果表明,在 OPSCC 中,高 FGFR3 表达与 p16 阴性状态和 mp53 表达相关,与更差的临床结局相关。FGFR3 和 mp53 在 OPSCC 中的生物学关系值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd20/7904228/e45992412887/pone.0247498.g001.jpg

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