Expression and clinicopathological significance of Nck1 in human astrocytoma progression

Int J Neurosci. 2019 Feb;129(2):171-178. doi: 10.1080/00207454.2018.1516655. Epub 2018 Nov 22.

Abstract

Objectives: Astrocytoma represents most noted malignancy of the brain. The overall survival rate of patients with progressive form remains dismal despite of the present clinical advancements. Search for biomarkers can open new avenues of therapeutic measures to curb the progressive astrocytic tumors. Nck1 is reported to be involved in actin cytoskeleton rearrangement and neuronal migration. Here, we have determined prognostic importance of Nck1 protein in astrocytoma progression. Temporal lobe epilepsy tissues were used as control.

Methods: Real time PCR was used to analyze Nck1 transcript expression while western blotting and immunohistochemistry techniques were used to study expression on translational levels. Protein expression in western blots was categorized as Nck1 positive and Nck1 negative. We further seen the prognostic significance of Nck1 in 246 glioblastoma tissue samples as visible from the TCGA database.

Results: We find Nck1 RNA and protein was upregulated significantly in high grade tissues as compared to low grade and control tissue samples (p < 0.05). Logrank test and Kaplan-Meier analysis signified the use of Nck1 as independent prognostic marker for astrocytoma progression and its expression levels were correlated with poor survival in surgically resected human tissue samples (Chi square = 10.7, p = 0.001). Further, glioblastoma was noticed to be predominant at frontal and temporal lobe.

Conclusion: On account of it's over expression, Nck1 appears as possible biomarker for astrocytoma progression and may serve as an important therapeutic target. Prominent origin of glioblastoma at frontal and temporal lobe suggests possible involvement of tissue specific developmental or transcriptional factors in origin of tumors.

Keywords: Nck1; astrocytoma; glioblastoma; prognostic marker.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Astrocytoma / diagnosis
  • Astrocytoma / metabolism*
  • Biomarkers, Tumor / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oncogene Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Nck protein
  • Oncogene Proteins