Abstract
The family with sequence similarity 83, member D (FAM83D) gene has been proposed as a new prognostic marker for breast cancer. Here we further evaluate the prognostic significance of FAM83D expression in different breast cancer subtypes using a meta-analysis. Patients with higher FAM83D mRNA levels have significantly decreased overall and metastatic relapse-free survival, particularly in the group of patients with ER-positive, or luminal subtype tumors. We also assessed FAM83D alterations and its prognostic significance across 22 human cancer types using The Cancer Genome Atlas (TCGA). FAM83D is frequently gained in the majority of human cancer types, resulting in the elevated expression of FAM83D. Higher levels of FAM83D mRNA expression are significantly associated with decreased overall survival in several cancer types. Finally, we demonstrate that TP53 mutation in human cancers is coupled to a significant increase in the expression of FAM83D, and that a higher level of FAM83D expression is positively correlated with an increase in genome instability in many cancer types. These results identify FAM83D as a potential novel oncogene across multiple human cancer types.
Highlights
Cancer is a complex and intrinsically heterogeneous disease in which patients may exhibit similar symptoms, and appear to have the same disease, for entirely different genetic reasons [1, 2, 3]
We recently identified FAM83D as a novel oncogene for breast cancer (BC) by demonstrating that higher FAM83D expression is significantly correlated with shorter disease- and distant metastasis-free surivival in BC patients, and that forced expression of FAM83D in vitro promotes BC cell proliferation, migration and invasion, while FAM83D depletion by shRNA leads to cell death [4]
Consistent with the results of the previous study [4], we found that higher levels of FAM83D were significantly associated with shorter overall and metastatic relapse-free survival, in patients with Estrogen receptor (ER)+ and luminal subtype tumors
Summary
Cancer is a complex and intrinsically heterogeneous disease in which patients may exhibit similar symptoms, and appear to have the same disease, for entirely different genetic reasons [1, 2, 3]. Microarray and generation sequencing technologies have been invaluable tools for deconvoluting the heterogeneity and complexity of somatic cancer genetics. These technologies are facilitating development of a catalogue of genomic changes with which to identify new biomarkers for the diagnosis, prognosis, and prediction of therapeutic response, and the discovery of new therapeutic targets. The family with sequence similarity 83, member D (FAM83D) gene is located on chromosome 20q, a region that is frequently amplified in various types of human cancer. We utilized the TCGA database to assess whether overexpression of FAM83D correlates with genetic instability (e.g. the fraction of cancer genomes with copy number alteration and mutation frequencies)
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