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Clinical and pathological findings in neurolymphomatosis: Preliminary association with gene expression profiles in sural nerves. | LitMetric

AI Article Synopsis

  • - This study investigates the molecular pathways involved in neurolymphomatosis (NL), a condition affecting the peripheral nervous system, focusing on clinical observations and gene expression analysis in nerve biopsies from NL patients and those with inflammatory neuropathies as controls.
  • - Researchers categorized NL patients into three neuropathy types based on symptoms and found notable differences in cellular infiltration patterns in nerve tissues between these forms.
  • - The study identified significant changes in gene expression, with 115 up-regulated and 1151 down-regulated genes, highlighting potential biomarkers like ACTA1 and DES, which may indicate a shift to a more aggressive phenotype in NL, possibly contributing to a worse prognosis.

Article Abstract

Although inflammation appears to play a role in neurolymphomatosis (NL), the mechanisms leading to degeneration in the peripheral nervous system are poorly understood. The purpose of this exploratory study was to identify molecular pathways underlying NL pathogenesis, combining clinical and neuropathological investigation with gene expression (GE) studies. We characterized the clinical and pathological features of eight patients with NL. We further analysed GE changes in sural nerve biopsies obtained from a subgroup of NL patients (n=3) and thirteen patients with inflammatory neuropathies as neuropathic controls. Based on the neuropathic symptoms and signs, NL patients were classified into three forms of neuropathy: chronic symmetrical sensorimotor polyneuropathy (SMPN, n=3), multiple mononeuropathy (MN, n=4) and acute motor-sensory axonal neuropathy (AMSAN, n=1). Predominantly diffuse malignant cells infiltration of epineurium was present in chronic SMPN, whereas endoneurial perivascular cells invasion was observed in MN. In contrast, diffuse endoneurium malignant cells localization occurred in AMSAN. We identified alterations in the expression of 1266 genes, with 115 up-regulated and 1151 down-regulated genes, which were mainly associated with ribosomal proteins (RP) and olfactory receptors (OR) signaling pathways, respectively. Among the top up-regulated genes were actin alpha 1 skeletal muscle (ACTA1) and desmin (DES). Similarly, in NL nerves ACTA1, DES and several RPs were highly expressed, associated with endothelial cells and pericytes abnormalities. Peripheral nerve involvement may be due to conversion towards a more aggressive phenotype, potentially explaining the poor prognosis. The candidate genes reported in this study may be a source of clinical biomarkers for NL.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9549065PMC
http://dx.doi.org/10.3389/fonc.2022.974751DOI Listing

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