Abstract
BackgroundOvarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian carcinogenesis and identify novel prognostic biomarkers.MethodsHere, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian carcinomas (n = 206) using immunohistochemistry (IHC).ResultsWe provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 chain (COL3A1), G protein-coupled receptor 158 (GPR158) and PITH domain containing 1 (PITHD1). Kaplan-Meier survival analysis revealed that COL3A1 expression was associated with shorter overall survival in the four major histotypes of epithelial ovarian carcinoma patients (P value = 0.026, HR = 2.99 (95% CI 1.089–8.19)). Furthermore, GPR158 and PITHD1 were shown to be histotype-specific prognostic biomarkers, with elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival (P value = 0.00043, HR = 6.13 (95% CI 1.98–18.98)), and an association with lower PITHD1 protein expression and unfavorable overall and disease-specific survival in clear-cell ovarian carcinoma patients (P value = 0.012, HR = 0.22 (95% CI 0.058–0.80); P value = 0.003, HR = 0.17 (95% CI 0.043–0.64)).ConclusionsThe novel biomarkers identified here may improve prognostication at the time of diagnosis and may assist in the development of future individualized therapeutic strategies for ovarian carcinoma patients.
Highlights
Ovarian cancer is the main cause of gynecological cancer-associated death
Patients and tumor samples Full-face formalin-fixed paraffin-embedded (FFPE) specimens were obtained from the Departments of Clinical Pathology at hospitals in Western Sweden for 206 earlystage primary invasive ovarian carcinoma patients diagnosed between 1994 and 2006, of which 95 samples corresponded to fresh-frozen tumor samples previously analyzed by RNA sequencing (RNA-seq) [13]
For Endometrioid ovarian carcinoma (EC), 1440 and 522 genes, and 3557 and 1827 genes for Clear-cell ovarian carcinoma (CCC) were associated with Overall survival (OS) and Disease-specific survival (DSS)
Summary
Ovarian cancer is the main cause of gynecological cancer-associated death. 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Engqvist et al BMC Cancer (2019) 19:928 to chemotherapy, disease progression and relapse of epithelial ovarian cancer [5]. It may not be suitable for the detection of early-stage ovarian cancer nor the MC histotype [5,6,7]. Additional serum biomarkers, such as CA 19–9, CA 15–3, CA 72–4 and CEA are routinely used in clinical practice [8]. High expression of aquaporin-1 (AQP1) in MC and EC, and low expression of AQP1 in CCC were associated with unfavorable prognosis [12]
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