Abstract
BackgroundFBXO11, a member of the F-box protein family, regulates the cell-cycle by promoting the degradation of Bcl-6 and p53. This protein has been implicated in the progression of several cancers, including renal cell carcinoma (RCC). The aim of this study was to determine the prognostic role of FBXO11 in the clinical outcome of RCC patients.MethodsFBXO11 mRNA expression was analysed in normal and RCC tissue microarrays of the Oncomine database. In addition, the in situ expression levels of stromal FBXO11 protein were assessed in primary RCC tissues from 227 patients (training and validation cohorts) using immunohistochemistry (IHC). Kaplan Meier and Cox regression analyses were used to determine the association between FBXO11 expression and cliniopathological factors. A nomogram was established using the significant prognostic factors to predict overall survival (OS) of RCC patients after one, three and 5 years.ResultsIn the Oncomine database, FBXO11 mRNA levels were lower in normal tissues than in cancer tissues, including clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), hereditary ccRCC, non-hereditary ccRCC, VHL mutant ccRCC and VHL wild-type ccRCC. In addition, FBXO11 expression was also significantly higher in metastatic kidney cancer than in primary cancer. Immunohistochemical analysis reported that 57.3% (86 of 150) of the training cohort and 57.1% (44 of 77) of the validation cohort were scored as having high FBXO11 staining density. FBXO11 expression was significantly associated with Fuhrman grade (p = 0.003), UISS score (p = 0.021) and age (p = 0.048) in the training cohort. Furthermore, Kaplan-Meier survival analysis showed that higher FBXO11 levels, T stage, UISS scores and SSIGN score were associated with poor OS in ccRCC patients. Multivariate Cox analysis demonstrated that higher FBXO11 levels and higher UISS score were independent prognostic indicators for OS. Nomogram, calibration plots, AUC values and the C-index showed that the predictive accuracy of conventional prognostic models, including UISS score and SSIGN score, was improved when FBXO11 expression was added.ConclusionsFBXO11 expression was closely related to RCC malignancy and poor prognosis, indicating its potential as a prognostic marker as well as a therapeutic target for RCC.
Highlights
FBXO11, a member of the F-box protein family, regulates the cell-cycle by promoting the degradation of Bcl-6 and p53
Higher FBXO11 mRNA levels were observed in kidney cancer tissues We analysed the FBXO11 levels in the Jones Renal microarray dataset from the Oncomine dataset [17]
FBXO11 expression was significantly lower in normal tissues than in cancer tissues (23 clear cell renal cell carcinoma (RCC) (ccRCC) and 11 papillary renal cell carcinoma (pRCC) samples) (P < 0.001, F = 14.03, Fig. 1a)
Summary
FBXO11, a member of the F-box protein family, regulates the cell-cycle by promoting the degradation of Bcl-6 and p53. This protein has been implicated in the progression of several cancers, including renal cell carcinoma (RCC). An estimated 65,340 new cases of kidney cancer and renal pelvic cancer, and 14,970 deaths relating to these diseases were projected for 2018 in the United States alone [3]. One-third of clear cell RCC (ccRCC) patients are diagnosed when the cancer has already metastasized, and indicates poor prognosis. The molecular mechanisms underlying the metastasis and progression of kidney cancer need to be elucidated in order to improve its prognosis
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