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Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer-A

Marclesson Alves1, Daniela de Paula Borges2, Aline Kimberly1,2

  • 1Department of Pathology, Federal University of Ceará, Fortaleza, Brazil.

Frontiers in Oncology
|March 26, 2021
PubMed
Abstract

Insights

Glycogen Synthase Kinase-3 beta (GSK-3β) expression correlates with advanced lung adenocarcinoma stages and poorer survival. A novel histological score for GSK-3β may aid in assessing prognosis and guiding future research on its interaction with PTEN.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Glycogen Synthase Kinase-3 beta (GSK-3β) is a key regulator of cellular processes, including metabolism, signaling, and protein structure.
  • GSK-3β influences pro-oncogene phosphorylation and programmed cell death-ligand 1 (PD-L1) regulation.
  • This study explores the relationship between GSK-3β expression and critical molecular features in lung adenocarcinoma.

Purpose of the Study:

  • To investigate the correlation between GSK-3β expression and PD-L1 score, PTEN expression, and driver mutations in lung adenocarcinoma.
  • To evaluate the potential of GSK-3β as a prognostic biomarker for overall survival in lung adenocarcinoma patients.
  • To establish a histological scoring system for GSK-3β expression in resected lung cancer tissues.

Main Methods:

  • Analysis of 95 lung cancer specimens (biopsies and surgical resections).
  • Immunohistochemistry to assess GSK-3β, PTEN, and PDL1 expression.
  • Evaluation of epidemiological data, molecular characteristics, and clinical staging from medical records.

Main Results:

  • GSK-3β expression was predominantly cytoplasmic, with 78% of tumors showing positivity, often associated with advanced stages (84% in Stage III/IV).
  • A significant association was found between GSK-3β and PTEN expression (p=0.021), particularly with higher GSK-3β intensity (p≤0.013).
  • GSK-3β positive tumors with high histological scores indicated worse overall survival.

Conclusions:

  • Histological patterns of GSK-3β expression were identified, and its potential as an overall survival marker was confirmed through a simple histological score.
  • The role of GSK-3β expression as an immune response biomarker requires further investigation.
  • Future research will focus on elucidating the interaction between GSK-3β and PTEN in lung adenocarcinoma.
Keywords:
glycogen synthase kinase-3 beta (GSK-3 beta)immunotherapylung cancernon-small cell carcinomaphosphatase and tensin homolog deleted on chromosome 10 (PTEN)programmed death-ligand 1 (PD-L1)

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