Characterization of FGD5 Expression in Primary Breast Cancers and Lymph Node Metastases

Abstract

Faciogenital dysplasia 5 ( FGD5) amplification drives tumor cell proliferation, and is present in 9.5% of breast cancers. We describe FGD5 expression, assess associations between FGD5 amplification and FGD5 expression, and assess FGD5 expression in relation to proliferation and prognosis. FGD5 immunohistochemistry was done on primary tumors ( n=829) and lymph node metastases ( n=231) from a cohort of Norwegian patients. We explored associations between FGD5 amplification, FGD5 expression, and proliferation, and analyzed the prognostic value of FGD5 expression by estimating cumulative risks of death and hazard ratios (HRs). We identified nuclear and cytoplasmic expression in 64% and 73% of primary tumors, respectively, and found an association between gene amplification and nuclear expression ( p=0.02). The proportion of cases with FGD5 expression was higher in lymph node metastases, compared with primary tumors ( p=0.004 for nuclear and p=0.001 for cytoplasmic staining). Neither proliferation nor prognosis was associated with FGD5 expression (age-adjusted HR 1.12 [95% confidence interval = 0.89-1.41] for nuclear expression; and 0.88 [95% CI = 0.70-1.12] for cytoplasmic expression). FGD5 is expressed in a high proportion of breast cancers and lymph node metastases. There was a correlation between FGD5 amplification and nuclear expression, but no association between FGD5 expression and proliferation or prognosis.

LncRNA FGD5-AS1 acts as a competing endogenous RNA for miRNA-223 to lessen oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury

“…The expression of FGD5-AS1 was reduced significantly in neurons subjected to OGD/R and overexpression of FGD5-AS1 could notably weaken neurons injury caused by OGD/R. FGD5 belongs to the Rho guanine nucleotide exchange factor (Rho GEF) family [8,16] and has been demonstrated to regulate proangiogenic action of VEGF in vascular endothelial cells [8]. Rho GEFs could activate Rho GTPases which modulate cytoskeleton and complicated in various cellular processes including gene expression, cell cycle progression as well as cell motility [16].…”

“…FGD5 belongs to the Rho guanine nucleotide exchange factor (Rho GEF) family [8,16] and has been demonstrated to regulate proangiogenic action of VEGF in vascular endothelial cells [8]. Rho GEFs could activate Rho GTPases which modulate cytoskeleton and complicated in various cellular processes including gene expression, cell cycle progression as well as cell motility [16]. Many Rho GEFs have been reported to be associated with the development of ischemic stroke or other cardiovascular disease, such as ARHGEF10 [9], Arhgef1 [2] etc.…”

The faciogenital dysplasia gene FGD5 is differentially expressed in non-small cell lung cancer and associates with patient survival.

“…A study of 430 breast tumors found that FGD1 was amplified in 9.5% of all breast cancers surveyed, with higher cumulative risk of death from breast cancer among cases with FGD5 amplification 12 . In a separate study of 829 primary breast cancers, proportion of cancers with FGD5 expression was significantly higher with in patients with metastasis to the lymph nodes 13 . There was also some association between FGD5 amplification and nuclear localization of FGD5 13 .…”

“…In a separate study of 829 primary breast cancers, proportion of cancers with FGD5 expression was significantly higher with in patients with metastasis to the lymph nodes 13 . There was also some association between FGD5 amplification and nuclear localization of FGD5 13 . An anti-sense non-coding RNA, FGD5-AS1 is described as possessing perturbed expression in multiple cancers, including in colorectal cancer 14 and in non-small cell lung cancer (NSCLC) 15,16 .…”

Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer

“…More recent integrative analysis using 52 gene expression signatures that measure oncogenic signaling pathways identified a limited number of genes that are amplified and overexpressed in aggressive luminal subtype tumors. Among these genes, a subset (FGD5, METTL6, CPT1A, DTX3, MRPS23, EIF2S2, EIF6, and SLC2A10) was found to be essential for cell growth and, in some instances, correlated with clinical outcome [ 99 , 103 , 104 , 105 ]. This study further suggests that not only do LumA and LumB tumors express unique mutation profiles, but that these alterations result in distinct patterns of oncogenic signaling beyond differences in proliferation.…”