High expression of FGD3, a putative regulator of cell morphology and motility, is prognostic of favorable outcome in multiple cancers

Scooter Willis, Yuliang Sun, Mark Abramovitz, Teng Fei, Brandon Young, Xiaoqian Lin, Min Ni, Justin Achua, Meredith M. Regan, Kathryn P. Gray, Robert Gray, Victoria Wang, Bradley Long, Roswitha Kammler, Joseph A. Sparano, Casey Williams, Lori J. Goldstein, Roberto Salgado, Sherene Loi, Giancarlo PruneriGiuseppe Viale, Myles Brown, Brian Leyland-Jones

Research output: Contribution to journalArticle

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Abstract

Purpose 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. Methods 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 FGD3 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. Results A meta-analysis of Cox regression of FGD3 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 FGD3 as a biomarker for freedom from recurrence was evaluated in the Breast InternationalGroup1-98(BIG1-98; 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 P value in five ER-positive cohorts showed that FGD3 (P = 3.8E-14) outperformed MKI67 (P = 1.06E-8) and AURKA (P = 2.61E-5). A comparison of the Stouffer P value in four ER-negative cohorts showed that FGD3 (P = 3.88E-5) outperformed MKI67 (P = .477) and AURKA (P = .820).

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalJCO Precision Oncology
Volume2017
Issue number1
DOIs
StatePublished - Jan 1 2017

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Cell Movement
Breast Neoplasms
Estrogen Receptors
Neoplasms
Aurora Kinase A
letrozole
Atlases
Messenger RNA
Meta-Analysis
Biomarkers
Aarskog Syndrome
Genome
Genes
Recurrence
Survival
Tamoxifen
Combination Drug Therapy
Breast

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

High expression of FGD3, a putative regulator of cell morphology and motility, is prognostic of favorable outcome in multiple cancers. / Willis, Scooter; Sun, Yuliang; Abramovitz, Mark; Fei, Teng; Young, Brandon; Lin, Xiaoqian; Ni, Min; Achua, Justin; Regan, Meredith M.; Gray, Kathryn P.; Gray, Robert; Wang, Victoria; Long, Bradley; Kammler, Roswitha; Sparano, Joseph A.; Williams, Casey; Goldstein, Lori J.; Salgado, Roberto; Loi, Sherene; Pruneri, Giancarlo; Viale, Giuseppe; Brown, Myles; Leyland-Jones, Brian.

In: JCO Precision Oncology, Vol. 2017, No. 1, 01.01.2017, p. 1-13.

Research output: Contribution to journalArticle

Willis, S, Sun, Y, Abramovitz, M, Fei, T, Young, B, Lin, X, Ni, M, Achua, J, Regan, MM, Gray, KP, Gray, R, Wang, V, Long, B, Kammler, R, Sparano, JA, Williams, C, Goldstein, LJ, Salgado, R, Loi, S, Pruneri, G, Viale, G, Brown, M & Leyland-Jones, B 2017, 'High expression of FGD3, a putative regulator of cell morphology and motility, is prognostic of favorable outcome in multiple cancers', JCO Precision Oncology, vol. 2017, no. 1, pp. 1-13. https://doi.org/10.1200/PO.17.00009
Willis, Scooter ; Sun, Yuliang ; Abramovitz, Mark ; Fei, Teng ; Young, Brandon ; Lin, Xiaoqian ; Ni, Min ; Achua, Justin ; Regan, Meredith M. ; Gray, Kathryn P. ; Gray, Robert ; Wang, Victoria ; Long, Bradley ; Kammler, Roswitha ; Sparano, Joseph A. ; Williams, Casey ; Goldstein, Lori J. ; Salgado, Roberto ; Loi, Sherene ; Pruneri, Giancarlo ; Viale, Giuseppe ; Brown, Myles ; Leyland-Jones, Brian. / High expression of FGD3, a putative regulator of cell morphology and motility, is prognostic of favorable outcome in multiple cancers. In: JCO Precision Oncology. 2017 ; Vol. 2017, No. 1. pp. 1-13.
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abstract = "Purpose 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. Methods 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 FGD3 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. Results A meta-analysis of Cox regression of FGD3 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 FGD3 as a biomarker for freedom from recurrence was evaluated in the Breast InternationalGroup1-98(BIG1-98; 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 P value in five ER-positive cohorts showed that FGD3 (P = 3.8E-14) outperformed MKI67 (P = 1.06E-8) and AURKA (P = 2.61E-5). A comparison of the Stouffer P value in four ER-negative cohorts showed that FGD3 (P = 3.88E-5) outperformed MKI67 (P = .477) and AURKA (P = .820).",
author = "Scooter Willis and Yuliang Sun and Mark Abramovitz and Teng Fei and Brandon Young and Xiaoqian Lin and Min Ni and Justin Achua and Regan, {Meredith M.} and Gray, {Kathryn P.} and Robert Gray and Victoria Wang and Bradley Long and Roswitha Kammler and Sparano, {Joseph A.} and Casey Williams and Goldstein, {Lori J.} and Roberto Salgado and Sherene Loi and Giancarlo Pruneri and Giuseppe Viale and Myles Brown and Brian Leyland-Jones",
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T1 - High expression of FGD3, a putative regulator of cell morphology and motility, is prognostic of favorable outcome in multiple cancers

AU - Willis, Scooter

AU - Sun, Yuliang

AU - Abramovitz, Mark

AU - Fei, Teng

AU - Young, Brandon

AU - Lin, Xiaoqian

AU - Ni, Min

AU - Achua, Justin

AU - Regan, Meredith M.

AU - Gray, Kathryn P.

AU - Gray, Robert

AU - Wang, Victoria

AU - Long, Bradley

AU - Kammler, Roswitha

AU - Sparano, Joseph A.

AU - Williams, Casey

AU - Goldstein, Lori J.

AU - Salgado, Roberto

AU - Loi, Sherene

AU - Pruneri, Giancarlo

AU - Viale, Giuseppe

AU - Brown, Myles

AU - Leyland-Jones, Brian

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Purpose 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. Methods 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 FGD3 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. Results A meta-analysis of Cox regression of FGD3 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 FGD3 as a biomarker for freedom from recurrence was evaluated in the Breast InternationalGroup1-98(BIG1-98; 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 P value in five ER-positive cohorts showed that FGD3 (P = 3.8E-14) outperformed MKI67 (P = 1.06E-8) and AURKA (P = 2.61E-5). A comparison of the Stouffer P value in four ER-negative cohorts showed that FGD3 (P = 3.88E-5) outperformed MKI67 (P = .477) and AURKA (P = .820).

AB - Purpose 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. Methods 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 FGD3 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. Results A meta-analysis of Cox regression of FGD3 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 FGD3 as a biomarker for freedom from recurrence was evaluated in the Breast InternationalGroup1-98(BIG1-98; 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 P value in five ER-positive cohorts showed that FGD3 (P = 3.8E-14) outperformed MKI67 (P = 1.06E-8) and AURKA (P = 2.61E-5). A comparison of the Stouffer P value in four ER-negative cohorts showed that FGD3 (P = 3.88E-5) outperformed MKI67 (P = .477) and AURKA (P = .820).

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