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FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

ABSTRACT: Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis.

SUBMITTER: Martinez-Aranda A

PROVIDER: S-EPMC4792555 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

Martínez-Aranda Antonio A Hernández Vanessa V Guney Emre E Muixí Laia L Foj Ruben R Baixeras Núria N Cuadras Daniel D Moreno Víctor V Urruticoechea Ander A Gil Miguel M Oliva Baldo B Moreno Ferran F González-Suarez Eva E Vidal Noemí N Andreu Xavier X Seguí Miquel A MA Ballester Rosa R Castella Eva E Sierra Angels A

Oncotarget 20151201 42

Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24 ...[more]

PMID: 26497551

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Project description:Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In this review, we summarize the findings of recent clinical research studies on biomarkers detected in samples obtained from patients with lung cancer bone metastasis. These markers include the following: (1) bone resorption-associated markers, such as N-terminal telopeptide (NTx)/C-terminal telopeptide (CTx), C-terminal telopeptide of type I collagen (CTx-I), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), pyridinoline (PYD), and parathyroid hormone related peptide (PTHrP); (2) bone formation-associated markers, including total serum alkaline phosphatase (ALP)/bone specific alkaline phosphatase(BAP), osteopontin (OP), osteocalcin (OS), amino-terminal extension propeptide of type I procollagen/carboxy-terminal extension propeptide of type I procollagen (PICP/PINP); (3) signaling markers, including epidermal growth factor receptor/Kirsten rat sarcoma/anaplastic lymphoma kinase (EGFR/KRAS/ALK), receptor activator of nuclear factor κB ligand/receptor activator of nuclear factor κB/osteoprotegerin (RANKL/RANK/OPG), C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4), complement component 5a receptor (C5AR); and (4) other potential markers, such as calcium sensing receptor (CASR), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2), cytokeratin 19 fragment/carcinoembryonic antigen (CYFRA/CEA), tissue factor, cell-free DNA, long non-coding RNA, and microRNA. The prognostic value of these markers is also investigated. Furthermore, we listed some clinical trials targeting hotspot biomarkers in advanced lung cancer referring for their therapeutic effects.

Dataset Information

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

Publications

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

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