High Expression of FGD3, a Putative Regulator of Cell Morphology and Motility, Is Prognostic of Favorable Outcome in Multiple Cancers.
meta_analysis · Level I
Where this comes from
- Record sourced from PubMed, PMID 32913979.
- Also identified by DOI 10.1200/PO.17.00009 and PMC identifier 7446538.
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Abstract
Identification of single-gene biomarkers that are prognostic of outcome can shed new insights on the molecular mechanisms that drive breast cancer and other cancers. Exploratory analysis of 20,464 single-gene messenger RNAs (mRNAs) in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) discovery cohort indicates that low expression of <i>FGD3</i> mRNA is prognostic for poor outcome. Prognostic significance of faciogenital dysplasia 3 (FGD3), SUSD3, and other single-gene proliferation markers was evaluated in breast cancer and The Cancer Genome Atlas (TCGA) cohorts. A meta-analysis of Cox regression of <i>FGD3</i> mRNA as a continuous variable for overall survival of estrogen receptor (ER)-positive samples in METABRIC discovery, METABRIC validation, TCGA breast cancer, and Combination Chemotherapy in Treating Women With Breast Cancer (E2197) cohorts resulted in a combined hazard ratio (HR) of 0.69 (95% CI, 0.63 to 0.75), indicating better outcome with high expression. In the ER-negative samples, the combined meta-analysis HR was 0.72 (95% CI, 0.63 to 0.82), suggesting that FGD3 is prognostic regardless of ER status. The potential of <i>FGD3</i> as a biomarker for freedom from recurrence was evaluated in the Breast International Group 1-98 (BIG 1-98; Letrozole or Tamoxifen in Treating Postmenopausal Women With Breast Cancer) study (HR, 0.85; 95% CI, 0.76 to 0.93) for breast cancer-free interval. In the Hungarian Academy of Science (HAS) breast cancer cohort, splitting on the median had an HR of 0.49 (95% CI, 0.42 to 0.58) for recurrence-free survival. A comparison of the Stouffer <i>P</i> value in five ER-positive cohorts showed that FGD3 (<i>P</i> = 3.8<sup>E-14</sup>) outperformed MKI67 (<i>P</i> = 1.06<sup>E-8</sup>) and AURKA (<i>P</i> = 2.61<sup>E-5</sup>). A comparison of the Stouffer <i>P</i> value in four ER-negative cohorts showed that FGD3 (<i>P</i> = 3.88<sup>E-5</sup>) outperformed MKI67 (<i>P</i> = .477) and AURKA (<i>P</i> = .820). <i>FGD3</i> was previously shown to inhibit cell migration. FGD3 mRNA is regulated by <i>ESR1</i> and is associated with favorable outcome in six distinct breast cancer cohorts and four TCGA cancer cohorts. This suggests that FGD3 is an important clinical biomarker.