Expression of Numb and Gli1 in malignant pleural mesothelioma and their clinical significance

J Cancer Res Ther. 2018 Jul-Sep;14(5):970-976. doi: 10.4103/0973-1482.180614.

Abstract

Aim of study: Malignant pleural mesothelioma (MPM) is a highly lethal and refractory to multimodal treatment tumor. Numb is considered as a tumor suppressor playing critical roles in determining cell fate and has been shown to target the oncogenic transcription factor Gli1 for Itch-dependent ubiquitination, resulting in suppression of the oncogenic sonic hedgehog signaling in medulloblastoma. This study was designed to analysis the role of Numb and Gli1 in MPM.

Materials and methods: Tissues of 61 MPM patients and 22 normal pleura as control were investigated. Numb and Gli1 expression were evaluated by immunohistochemistry. The associations with clinical and pathological parameters of the two markers were statistically analyzed, and the correlation between them was also demonstrated.

Results: The expression levels of Numb with nuclear Gli1 exhibited a significant inverse correlation (r = -0.361 P < 0.05). In addition, Numb has an inverse correlation with ki-67 labeling index (P < 0.05), and nuclear Gli1 was found in associated with the tumor International Mesothelioma Interest Group-stage (P < 0.05). The overall survival was influenced by the expression of Numb (P < 0.05) and histological subtype (P < 0.05), further regression analysis showed that only histological subtype has a prognostic influence on survival (P < 0.05).

Conclusion: The results provide new evidence of Numb and Gli1 on the clinical characteristics of MPM, which may be helpful in clinical diagnosis and targeted therapy. Further research with larger sample size is needed.

Keywords: Clinical significance; Gli1; Numb; malignant pleural mesothelioma.

MeSH terms

  • Aged
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Membrane Proteins / genetics*
  • Mesothelioma / diagnosis
  • Mesothelioma / genetics*
  • Mesothelioma / pathology
  • Mesothelioma / therapy
  • Mesothelioma, Malignant
  • Middle Aged
  • Molecular Targeted Therapy
  • Nerve Tissue Proteins / genetics*
  • Pleural Neoplasms / diagnosis
  • Pleural Neoplasms / genetics*
  • Pleural Neoplasms / pathology
  • Pleural Neoplasms / therapy
  • Prognosis
  • Zinc Finger Protein GLI1 / genetics*

Substances

  • GLI1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Numb protein, human
  • Zinc Finger Protein GLI1