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Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden.

ABSTRACT: Neurofibromatosis type 1 (NF1) is the most common tumor predisposition disorder affecting 1/3500 worldwide. Patients are at risk of developing benign (neurofibromas) and malignant peripheral nerve sheath tumors (MPNST). The AXL receptor tyrosine kinase has been implicated in several kinds of cancers, but so far no studies have investigated the role of AXL in NF1 related tumorigenesis. Recently, the soluble fraction from the extracellular domain of AXL (sAXL) has been found in human plasma, and its level was correlated to poor prognosis in patients with renal cancer. Compared to normal human Schwann cells, a significantly high expression level of AXL was found in three of the four MPNST cell lines and two of the three primary MPNST tissues. Similarly, the level of sAXL in conditioned media corresponded to the protein and mRNA levels of AXL in the MPNST cell lines. Furthermore, in two different human MPNST xenograft models, the human sAXL could be detected in the mouse plasma. Its level was proportionate to the size of the xenograft tumors, while no human sAXL was detect prior to the formation of the tumors. Treatment with a newly developed photodynamic therapy, prevented further tumor growth and resulted in drastically reduced the levels of sAXL compared to that of the control group. Finally, the level of sAXL was significantly increased in patients with plexiform tumors compared to patients with only dermal neurofibromas, further supporting the role of sAXL as a marker for NF1 related tumor burden.

SUBMITTER: Johansson G

PROVIDER: S-EPMC4281253 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden.

Johansson Gunnar G Peng Po-Chun PC Huang Po-Yuan PY Chien Hsiung-Fei HF Hua Kuo-Tai KT Kuo Min-Liang ML Chen Chin-Tin CT Lee Ming-Jen MJ

PloS one 20141231 12

Neurofibromatosis type 1 (NF1) is the most common tumor predisposition disorder affecting 1/3500 worldwide. Patients are at risk of developing benign (neurofibromas) and malignant peripheral nerve sheath tumors (MPNST). The AXL receptor tyrosine kinase has been implicated in several kinds of cancers, but so far no studies have investigated the role of AXL in NF1 related tumorigenesis. Recently, the soluble fraction from the extracellular domain of AXL (sAXL) has been found in human plasma, and i ...[more]

PMID: 25551830

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Project description:Neurofibromatosis type-1 (NF1) patients suffer from cutaneous and subcutaneous neurofibromas (CNF) and large plexiform neurofibromas (PNF). Whole gene deletions of the NF1 gene can cause a more severe phenotype compared to smaller intragenic changes. Two distinct groups of NF1 whole gene deletions are type-1 deletions and atypical deletions. Our aim was to assess volumes and averaged annual growth-rates of CNF and PNF in patients with NF1 whole gene deletions and to compare these with NF1 patients without large deletions of the NF1 gene. We retrospectively evaluated 140 whole-body MR examinations of 38 patients with NF1 whole gene deletions (type-1 group: n = 27/atypical group n = 11) and an age- and sex matched collective of 38 NF1-patients. Age-dependent subgroups were created (0-18 vs >18 years). Sixty-four patients received follow-up MRI examinations (NF1whole gene deletion n = 32/control group n = 32). Whole-body tumor-volumes were semi-automatically assessed (MedX, V3.42). Tumor volumes and averaged annual growth-rates were compared. Median tumor-burden was significantly higher in the type-1 group (418ml; IQR 77 - 950ml, p = 0.012) but not in the atypical group (356ml;IQR 140-1190ml, p = 0.099) when compared to the controls (49ml; IQR 11-691ml). Averaged annual growth rates were significantly higher in both the type-1 group (14%/year; IQR 45-36%/year, p = 0.004) and atypical group (11%/year; IQR 5-23%/year, p = 0.014) compared to the controls (4%/year; IQR1-8%/year). Averaged annual growth rates were significantly higher in pediatric patients with type-1 deletions (21%/year) compared with adult patients (8%/year, p = 0.014) and also compared with pediatric patients without large deletions of the NF1 gene (3.3%/year, p = 0.0015). NF1 whole gene deletions cause a more severe phenotype of NF1 with higher tumor burden and higher growth-rates compared to NF1 patients without large deletions of the NF1 gene. In particular, pediatric patients with type-1 deletions display a pronounced tumor growth.

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Dataset Information

Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden.

Publications

Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden.

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