SOD2- and NRF2-associated Gene Signature to Predict Radioresistance in Head and Neck Cancer.

Abstract

BACKGROUND:

We propose a novel prognostic biomarker-based strategy for increasing the efficacy of radiotherapy (RT) in head and neck squamous cell carcinoma (HNSCC).

MATERIALS AND METHODS:

We identified genes associated with superoxide dismutase 2 (SOD2) and nuclear factor erythroid-2-related factor 2 (NRF2) from gene-expression data of The Cancer Genome Atlas (TCGA) by calculating Pearson correlation. Patients were divided into two groups using hierarchical clustering. Colony-formation assay was performed to determine radioresistance in HNSCC cell line CAL27. Pathway analysis was conducted using The Database for Annotation, Visualization and Integrated Discovery (DAVID).

RESULTS:

We developed a 49-gene signature with SOD2- and NRF2-associated genes. Using mRNA expression data for the 49-gene signature, we performed hierarchical clustering to stratify patients into two subtypes, subtype A and B. In the TCGA cohort, subgroup A demonstrated a better prognosis than subgroup B in patients who received RT. The signature robustness was evaluated in other independent cohorts. We showed through colony-formation assay that depletion of SOD2 or NRF2 leads to increased radiosensitivity.

CONCLUSION:

We identified and validated a robust gene signature of SOD2- and NRF2-associated genes in HNSCC and confirmed their link to radioresistance using in vitro assay, providing a novel biomarker for the evaluation of HNSCC prognosis.

• Authors: Joo Kyung Noh, Seon Rang Woo, Miyong Yun, Min Kyeong Lee, Moonkyoo Kong, Soonki Min, Su Il Kim, Young Chan Lee, Young-Gyu Eun, Seong-Gyu Ko
• Journal: Cancer genomics & proteomics (Cancer Genomics Proteomics) 2021 Sep-Oct Vol. 18 Issue 5 Pg. 675-684 ISSN: 1790-6245 [Electronic] Greece
• PMID: 34479919 (Publication Type: Journal Article)
• Copyright: Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• NF-E2-Related Factor 2
• Superoxide Dismutase
• superoxide dismutase 2

Topics

• Female
• Humans
• Male
• Middle Aged
• NF-E2-Related Factor 2 (metabolism)
• Prognosis
• Squamous Cell Carcinoma of Head and Neck (genetics, pathology)
• Superoxide Dismutase (metabolism)