Abstract
There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 μg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.
Highlights
Cervical cancer (CC) is the third most common gynecologic malignancy and the fourth leading cause of death in women worldwide, with an estimated global incidence of 604,000 new cases in 2020 [1]
We identified apolipoprotein C-II (ApoC-II) as a potential predictor of postRT outcomes in patients with CC [5]
Further evaluation is needed to determine the practical usefulness of squamous cell carcinoma antigen (SCC-Ag) in the treatment strategy for CC. In this prospective multicenter cohort study, we evaluated the usefulness of ApoC-II, matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-2 (MMP2), and SCC-Ag, as prognostic serum biomarkers for patients with CC treated with RT
Summary
Cervical cancer (CC) is the third most common gynecologic malignancy and the fourth leading cause of death in women worldwide, with an estimated global incidence of 604,000 new cases in 2020 [1]. The standard treatment for locally advanced CC is definitive concurrent chemoradiotherapy (CCRT) [2], which results in a 3-year disease-free survival (DFS) of 65%–75% [2,3]. We have used surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry to identify serum protein biomarkers that had different protein expression patterns in healthy women and patients with CC. Low-density lipoproteins shrink after the release of lipids, and ApoC-II either reenters the circulation or is utilized by cancer cells [8]. In this prospective multicenter cohort study, we validated the usefulness of ApoC-II for the prediction of survival outcomes after RT in patients with advanced CC
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