Age-related copy number variations and expression levels of F-box protein FBXL20 predict ovarian cancer prognosis

Abstract

About 70% of ovarian cancer (OvCa) cases are diagnosed at advanced stages (stage III/IV) with only 20–40% of them survive over 5 years after diagnosis. A reliably screening marker could enable a paradigm shift in OvCa early diagnosis and risk stratification. Age is one of the most significant risk factors for OvCa. Older women have much higher rates of OvCa diagnosis and poorer clinical outcomes. In this article, we studied the correlation between aging and genetic alterations in The Cancer Genome Atlas Ovarian Cancer dataset. We demonstrated that copy number variations (CNVs) and expression levels of the F-Box and Leucine-Rich Repeat Protein 20 ( FBXL20 ), a substrate recognizing protein in the SKP1-Cullin1-F-box-protein E3 ligase, can predict OvCa overall survival, disease-free survival and progression-free survival. More importantly, FBXL20 copy number loss predicts the diagnosis of OvCa at a younger age, with over 60% of patients in that subgroup have OvCa diagnosed at age less than 60 years. Clinicopathological studies further demonstrated malignant histological and radiographical features associated with elevated FBXL20 expression levels. This study has thus identified a potential biomarker for OvCa prognosis.

FBXL18 is required for ovarian cancer cell proliferation and migration through activating AKT signaling

“…FBXL10 has been reported to act as a crucial tumor accelerator in gastric cancer [26], colon cancer [27], and breast cancer [28]. Additionally, studies have indicated that upregulation of the FBXL20 protein level is associated with malignant histological features of OC and that the depletion of FBXL20 activity may improve OC clinical outcomes [29,30].…”

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers

“…Investigating TMPRSS2-ERG and their alternative partners revealed six (out of 29) African-derived fusions with novel PCa partners to ETV4, ERG and TMPRSS2 , including FBXO7 , LINC01525, GTF3C2 and NTNG1. Classified as a potential tumour suppressor gene, disruption of FBXO47 has been reported in breast, ovarian and renal cancers [ 58 , 59 ], while to the best of our knowledge this is the first report of LINCO1525 disruption in any cancer. GTF3C2 is one member of the general transcription factor III family, which has been reported as a prognostic factor in liver cancer [ 60 ].…”

TCR CDR3‐antigen chemical complementarity associated with poor ovarian cancer outcomes: A vestigial immune response to early cancer antigens?

“…This finding is in concordance with previously published results indicating that CN variation is a common mechanism whereby cancer cells alter gene expression, resulting in immune evasion and higher levels of proliferation. [ 20,21 ]…”

“…This finding is in concordance with previously published results indicating that CN variation is a common mechanism whereby cancer cells alter gene expression, resulting in immune evasion and higher levels of proliferation. [20,21] Observing these molecular changes and their correlations with reduced DFS, we sought to identify a specific AA sequence within MAGEB4 and TDRD1 responsible for the observed inverse relationship for the electrostatic CSs and DFS. However, fragmenting of TDRD1 revealed the opposing paradigm: high hydro CS for CDR3-TDRD1 Fragment 17 was associated with better DFS, replicated with two sources of CDR3s, the TCGA-OV WXS files and RNAseq files.…”