Epigenetic Regulations of Perineural Invasion in Head and Neck Squamous Cell Carcinoma

Abstract

Carcinomas of the oral cavity and oropharynx belong among the ten most common malignancies in the human population. The prognosis of head and neck squamous cell carcinoma (HNSCC) is determined by the degree of invasiveness of the primary tumor and by the extent of metastatic spread into regional and distant lymph nodes. Moreover, the level of the perineural invasion itself associates with tumor localization, invasion’s extent, and the presence of nodal metastases. Here, we summarize the current knowledge about different aspects of epigenetic changes, which can be associated with HNSCC while focusing on perineural invasion (PNI). We review epigenetic modifications of the genes involved in the PNI process in HNSCC from the omics perspective and specific epigenetic modifications in OSCC or other neurotropic cancers associated with perineural invasion. Moreover, we summarize DNA methylation status of tumor-suppressor genes, methylation and demethylation enzymes and histone post-translational modifications associated with PNI. The influence of other epigenetic factors on the HNSCC incidence and perineural invasion such as tobacco, alcohol and oral microbiome is overviewed and HPV infection is discussed as an epigenetic factor associated with OSCC and related perineural invasion. Understanding epigenetic regulations of axon growth that lead to tumorous spread or uncovering the molecular control of axon interaction with cancer tissue can help to discover new therapeutic targets for these tumors.

Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma

“…Several other studies demonstrated an association between the epigenetic regulation of specific candidate genes by altered DNA methylation and the development of PNI [42][43][44][45][46][47][48][49][50]. Still, the DNA methylation status in head and neck squamous cell carcinoma has not yet been studied sufficiently [50]. Consistent with these studies, genome-wide DNA hypomethylation was evident in ML A HNSCC at least in part due to truncating NSD1 mutations.…”

“…Moreover, the DNA methylation of the CDKN2A promoter was a more frequent event in aggressive prostatic tumors with PNI [41]. Several other studies demonstrated an association between the epigenetic regulation of specific candidate genes by altered DNA methylation and the development of PNI [42][43][44][45][46][47][48][49][50]. Still, the DNA methylation status in head and neck squamous cell carcinoma has not yet been studied sufficiently [50].…”

Prognostic DNA mutation and mRNA expression analysis of perineural invasion in oral squamous cell carcinoma

“…Especially, the hallmarks epithelial mesenchymal transition pathway overlapped with the DNA mutation mentioned above, TGFBR1 . EMT is a process by which polar epithelial cells are transformed into mesenchymal cells with a significantly enhanced ability to migrate and invade the surrounding tissues and already well known for its relationship with PNI in HNSCC 7 , 16 . There were strong expression of BDNF, TrkB, and p75NGFR in perineural tumor cells of human cutaneous squamous cell carcinoma 17 , and over-expression of TrkB results in altered expression of molecular mediators of EMT, including downregulation of E-cadherin and upregulation of Twist in HNSCC 18 .…”

ANXA6/TRPV2 axis promotes lymphatic metastasis in head and neck squamous cell carcinoma by inducing autophagy

“…However, the complex anatomical structure and concealability of the disease as well as the high demand for functional preservation make the choice of surgical approach more challenging, resulting in a low surgical cure rate and poor postoperative prognosis, with approximately 60% survival at 5 years [ 2 , 5 ]. Lymphatic metastasis (LM) and degree of primary tumor invasion are the main factors affecting the prognosis of HNSCC [ 6 ]. In previous studies, LM has been shown to be an independent prognostic factor for HNSCC [ 7 , 8 ].…”