Jeong Soo Young, Chung Joon-Yong, Byeon Sun-Ju, Kim Chul Jung, Lee Yoo-Young, Kim Tae-Joong, Lee Jeong-Won, Kim Byoung-Gie, Chae Ye Lin, Oh So Young, Choi Chel Hun
Departments of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Front Oncol. 2021 Jul 19;11:665595. doi: 10.3389/fonc.2021.665595. eCollection 2021.
In a previous study, a proteomic panel consisting of BCL-2, HER2, CD133, CAIX, and ERCC1 significantly predicted survival in patients with locally advanced cervical cancer. However, the prognostic significance of these proteins has not been assessed in early cervical cancer. The present study investigated the clinical significance and chemoradioresistance prediction power of these proteins in patients with early-stage cervical cancer.
BCL-2, HER2, CD133, CAIX, and ERCC1 expression was determined by the immunohistochemical staining of 336 cervical cancer tissue microarrays. The associations of these proteins with clinicopathologic characteristics and disease progression were assessed.
There was a trend of low CAIX expression (p=0.082) and high ERCC1 expression (p=0.059) in patients with a favorable response to adjuvant radiation. High HER2 expression was significantly associated with shorter disease-free survival (DFS) in the total group (5-year DFS of 80.1% . 92.2%, p=0.004). A prognostic significance remained in multivariate analysis (Hazard ratio, HR=2.10, p=0.029). In the adjuvant radiation group, low CAIX and high ERCC1 expression indicated significantly unfavorable DFS (75.0% . 89.0%, p=0.026 and 76.8% . 88.6%, p=0.022, respectively). Low CAIX expression remained an independent prognostic marker in multivariate analysis (HR=0.45, p=0.037). The combined molecular-clinical model using random survival forest method predicted DFS with improved power compared with that of the clinical variable model (C-index 0.77 . 0.71, p=0.006).
HER2, CAIX, and ERCC1 expression can be predictive protein markers for clinical outcomes in early cervical cancer patients treated primarily with radical surgery with or without adjuvant radiation.
在之前的一项研究中，由BCL-2、HER2、CD133、CAIX和ERCC1组成的蛋白质组学面板显著预测了局部晚期宫颈癌患者的生存率。然而，这些蛋白质在早期宫颈癌中的预后意义尚未得到评估。本研究调查了这些蛋白质在早期宫颈癌患者中的临床意义和预测放化疗耐药性的能力。
通过对336个宫颈癌组织微阵列进行免疫组织化学染色来确定BCL-2、HER2、CD133、CAIX和ERCC1的表达。评估这些蛋白质与临床病理特征和疾病进展的相关性。
对辅助放疗反应良好的患者中存在CAIX低表达趋势（p=0.082）和ERCC1高表达趋势（p=0.059）。HER2高表达与全组患者较短的无病生存期（DFS）显著相关（5年DFS为80.1%对92.2%，p=0.004）。多因素分析中仍具有预后意义（风险比，HR=2.10，p=0.029）。在辅助放疗组中，CAIX低表达和ERCC1高表达表明DFS显著较差（分别为75.0%对89.0%，p=0.026和76.8%对88.6%，p=0.022）。CAIX低表达在多因素分析中仍是独立的预后标志物（HR=0.45，p=0.037）。与临床变量模型相比，使用随机生存森林法的联合分子临床模型预测DFS的能力有所提高（C指数0.77对0.71，p=0.006）。
HER2、CAIX和ERCC1表达可作为主要接受根治性手术加或不加辅助放疗的早期宫颈癌患者临床结局的预测性蛋白质标志物。
