Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, United States.
Houston Eye Associates, Clinical Research Department, Houston, TX, United States.
Oral Oncol. 2020 Dec;111:104949. doi: 10.1016/j.oraloncology.2020.104949. Epub 2020 Aug 12.
Recurrence rates for head and neck squamous cell carcinoma (HNSCC) approach 50% at 5 years. Current staging fails to identify patients with a worse prognosis who might benefit from intensified treatment, which warrants improved prognostic biomarkers. The purpose of this retrospective case study is to identify potential prognostic biomarkers in patients with HNSCC including APE1 (DNA repair/redox gene regulator), NRF2 and PPARGC1A (redox gene regulators), SOD3 and DCN (antioxidant proteins).
Differential protein expression between benign, carcinoma in situ (CIS), and invasive HNSCC tissue specimens from 77 patients was assessed using immunohistochemistry. Protein expression was analyzed with multivariate, pair-wise, and Kaplan-Meier survival analyses to identify potential prognostic biomarkers. Utilizing The Cancer Genome Atlas's transcriptome database, pair-wise and survival analysis was performed to identify potential prognostic biomarkers.
APE1, NRF2, PPARGC1A, SOD3, and DCN expression in HNSCC in relation to, lymph node invasion, and patient survival were examined. Elevated APE1 protein expression in CIS corresponded with reduced survival (p = 0.0243). Increased APE1 gene expression in stage T4a HNSCC was associated with reduced patient survival (p < 0.015). Increased PPARGC1A in invasive tumor correlated with reduced survival (p = 0.0281). Patients with lymph node invasion at diagnosis had significantly increased APE1 protein in the primary sites (p < 0.05). Patients with poorly differentiated invasive tumors had reduced PPARGC1A in CIS proximal to the invasive tumor and had elevated DCN and SOD3 in proximal benign tissue (p < 0.05).
The expression of APE1, DCN, and SOD3 is a potential prognostic signature that identifies patients with worsened survival.
头颈部鳞状细胞癌（HNSCC）的复发率在 5 年内接近 50%。目前的分期方法无法识别预后较差的患者，这些患者可能受益于强化治疗，因此需要改进预后生物标志物。本回顾性病例研究的目的是确定 HNSCC 患者的潜在预后生物标志物，包括 APE1（DNA 修复/氧化还原基因调节剂）、NRF2 和 PPARGC1A（氧化还原基因调节剂）、SOD3 和 DCN（抗氧化蛋白）。
使用免疫组织化学评估 77 例患者的良性、原位癌（CIS）和侵袭性 HNSCC 组织标本之间的差异蛋白表达。通过多元、成对和 Kaplan-Meier 生存分析来分析蛋白表达，以确定潜在的预后生物标志物。利用癌症基因组图谱的转录组数据库，进行成对和生存分析，以确定潜在的预后生物标志物。
研究了 APE1、NRF2、PPARGC1A、SOD3 和 DCN 在 HNSCC 中与淋巴结侵犯和患者生存的关系。CIS 中 APE1 蛋白表达升高与生存时间缩短相关（p=0.0243）。T4a 期 HNSCC 中 APE1 基因表达增加与患者生存时间缩短相关（p<0.015）。侵袭性肿瘤中 PPARGC1A 增加与生存时间缩短相关（p=0.0281）。诊断时存在淋巴结侵犯的患者原发部位 APE1 蛋白显著增加（p<0.05）。分化不良的侵袭性肿瘤患者在靠近侵袭性肿瘤的 CIS 中 PPARGC1A 减少，在邻近良性组织中 DCN 和 SOD3 增加（p<0.05）。
APE1、DCN 和 SOD3 的表达是一种潜在的预后标志物，可识别生存时间恶化的患者。
