Cancer Cell Research (Online ISSN: 2161-2609)

Cancer Cell Research 2022 9(34) 841-855; published online  12 November 2022

Abstract: Background BRAF and NRAS mutations are two major somatic mutations extensively investigated in papillary thyroid cancer (PTC). However, much fewer studies have been conducted to investigate the underlying molecular mechanic difference caused by the two mutations. Methods Multi-level genomic data of 496 PTC samples and corresponding clinical data were all retrieved from TCGA database. Clinico-pathological factors and molecular dysregulations were compared between PTC samples with different BRAF and NRAS mutational status. Results BRAF and NRAS mutations were both significantly associated with histological diagnosis, extrathyroidal invasion and lymph node metastasis in PTC(all p < 0.01), and BRAF mutation might promote invasion and migration, while NRAS mutation works the otherwise. Neither DNA copy numbers(FDR < 0.01, fold change > 1.5) nor methylations(FDR < 0.01, |Δ| > 0.2) were significantly altered by these mutations, while mRNA dysregulations were commonly observed. Additionally, mRNAs differentially expressed in both BRAF and NRAS mutations tended to be dysregulated at reverse directions. T cell regulation was the major biological function of these reversely dysregulated mRNAs. Furthermore, Fibronectin was over-expressed in BRAF mutated while under-expressed in NRAS mutated patients(p=6.492×10-7). Conclusions The mRNA expression patterns were significantly reversed between BRAF and NRAS mutated PTC samples. These oppositely dysregulated mRNAs were significantly related to T lymph cell regulation and immune response.