Overexpression of RRM2 is related to poor prognosis in oral squamous cell carcinoma

Oral Dis. 2021 Mar;27(2):204-214. doi: 10.1111/odi.13540. Epub 2020 Jul 30.

Abstract

Objectives: Ribonucleotide reductase M2 (RRM2) is a rate-limiting enzyme involved in DNA repair and synthesis. This study aimed to investigate the expression level, clinicopathological significance, and prognostic value of RRM2 in oral squamous cell carcinoma (OSCC).

Materials and methods: Human OSCC tissue microarrays were used to detect the expression of RRM2, cancer stem cell (CSC) markers CD44 and aldehyde dehydrogenase 1 (ALDH1), and the epithelial-mesenchymal transition (EMT) marker Slug. The correlation of RRM2 expression with clinicopathological parameters was evaluated. The effects of RRM2 on cell proliferation, migration, and apoptosis were investigated.

Results: Compared with normal and dysplastic tissues, the expression of RRM2 in human primary OSCC was significantly increased, and its overexpression was correlated with advanced pathological grade. The overall survival rate of patients with high RRM2 expression was lower than that of patients with low RRM2 expression. The overexpression of RRM2 was significantly associated with OSCC recurrence, and its overexpression was correlated with the CSC markers CD44 and ALDH1 and the EMT marker Slug. The expression of RRM2 promotes the proliferation and migration of human OSCC cells and inhibits apoptosis.

Conclusion: Ribonucleotide reductase M2 may be a novel target in the diagnosis, prognosis, and therapy of OSCC.

Keywords: RRM2; TCGA; clinicopathologic significance; oral squamous cell carcinoma; overall survival; tissue microarray.

MeSH terms

  • Carcinoma, Squamous Cell* / genetics
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms*
  • Humans
  • Mouth Neoplasms* / genetics
  • Neoplasm Recurrence, Local
  • Prognosis
  • Ribonucleoside Diphosphate Reductase
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • ribonucleotide reductase M2
  • Ribonucleoside Diphosphate Reductase