Survivin/BIRC5 as a novel molecular effector at the crossroads of glucose metabolism and radioresistance in head and neck squamous cell carcinoma

Head Neck. 2024 Jul;46(7):1752-1765. doi: 10.1002/hed.27651. Epub 2024 Feb 2.

Abstract

Background: Metabolic reprogramming and abnormal glucose metabolism are hallmarks of head and neck squamous cell carcinoma (HNSCC). Certain oncogenes can promote cancer-related metabolic changes, but understanding their crosstalk in HNSCC biology and treatment is essential for identifying predictive biomarkers and developing target therapies.

Methods: We assessed the value of survivin/BIRC5 as a radioresistance factor potentially modulated by glucose for predicting therapeutic sensitivity and prognosis of HNSCC in a cohort of 32 patients. Additionally, we conducted in vitro experiments to explore the role of survivin/BIRC5 in glucose metabolism concerning radiation response.

Results: Tumoral BIRC5 expression is associated with serum glucose and predicts locoregional disease-free survival and lower BIRC5 mRNA levels are associated with better outcomes. Upregulation of BIRC5 by radiation depends on glucose levels and provokes a pro-tumoral and radioresistant phenotype in surviving cells.

Conclusions: Survivin/BIRC5 might be independently associated with the risk of recurrence in patients with HNSCC.

Keywords: HNSCC; glucose metabolism; radioresistance; radiotherapy; survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Cell Line, Tumor
  • Disease-Free Survival
  • Female
  • Glucose* / metabolism
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / pathology
  • Head and Neck Neoplasms* / radiotherapy
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Radiation Tolerance* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Squamous Cell Carcinoma of Head and Neck* / radiotherapy
  • Survivin* / genetics
  • Survivin* / metabolism

Substances

  • Survivin
  • BIRC5 protein, human
  • Glucose
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins