Abstract
BackgroundIn 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.Materials and MethodsBCL-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.ResultsThere 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% vs. 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% vs. 89.0%, p=0.026 and 76.8% vs. 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 vs. 0.71, p=0.006).ConclusionHER2, 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.
Highlights
Cervical cancer is the fourth most common malignancy and the leading cause of cancer-related death in women in developing countries [1]
We found that a panel of proteins, B cell lymphoma-2 (BCL-2), HER2, CD133, Carbonic anhydrase IX (CAIX), and Excision repair cross-complementing 1 (ERCC1), can be predictors of overall survival in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT) by calculating risk scores, which were the sum of estimated coefficients from age, cancer stage, and the protein panel [14]
We investigated the prognostic significance of BCL-2, HER2, CD133, CAIX, and ERCC1 expression in Operation and adjuvant treatment group
Summary
Cervical cancer is the fourth most common malignancy and the leading cause of cancer-related death in women in developing countries [1]. Radical hysterectomy and adjuvant radiation with or without chemotherapy is the primary treatment and performed if there are risk factors. Each patient has a varied response to adjuvant radiation and/or chemotherapy; the prediction of the response to each treatment is important. Several clinical factors that can predict the response to radiotherapy in cervical cancer have been investigated. Hyperthermia during radiotherapy can make cancer cells more sensitive and affect the outcome of radiotherapy [6] These factors alone cannot accurately predict chemoradiosensitivity. New markers with molecular approaches using genes or proteins are needed to predict the clinical outcomes of cancer patients more accurately. The present study investigated the clinical significance and chemoradioresistance prediction power of these proteins in patients with early-stage cervical cancer
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