HNSC, a dreadful opponent, has become one of the world's most deadly diseases. Treatment for HNSC is costly, has a long cycle, and is not affordable. The precise and early prediction of HNSC outcomes is critical for therapy options and prognosis improvement. Our present study focused on gene mutation and dysregulation expression in HNSC, expecting to identify essential biomarkers for HNSC.
In the present study, we explored the landscape of mutation and dysregulation in HNSC patients, showing that TP53, TTN, FAT1, CDKN2A, and MUC16 were the most predominant mutated genes. The mutation identification was consistent with Jiang et al. 14. Among human genes, TP53 is a critical tumor suppressor gene, with low expression in normal cells and high expression in malignant tumors, regulating cell proliferation, apoptosis, angiogenesis, and DNA repair 15. Mutated TP53 was found in various cancers and is correlated with reduced O.S. Furthermore, it showed that HNSC patients with TP53 mutations have a bleak prognosis than TP53-wildtype HNSC 16. Our present study also found that mutated TP53 is observed in HNSC.
Then, the dysregulated genes were identified, with 187 DEGs having more mutation sites. We conducted the PPI analysis on these DEGs, and two modules were identified. We further analyzed these DEGs in these modules by GO-BP and KEGG analyses. The DEGs in module A are involved in the PI3K-Akt signaling pathway, which is a classic intracellular signaling pathway regulating cell apoptosis, proan essential pathway that regulates cell apoptosis, prognosis, and metastasis in HNSC 17–19. The DEGs in module B participated in the cGMP-PKG signaling pathway. Tuttle et al. 20 demonstrated that the cGMP-PKG signaling pathway is one of the therapeutic targets of HNSC.
The DEGs of ACTN2, MYH1, MYH2, MYH7, and NEB in module B were significantly associated with O.S. in HNSC. ACTN2 is a member of the spectrin gene superfamily that includes varying groups of cytoskeletal proteins. In breast cancer patients, mutated ACTN2 was related to invasive ductal carcinoma and suggested a worse O.S. than ductal carcinoma in situ 21. Sun et al. 22 demonstrated that ACTN2 is one of the hub genes selected by bioinformatics methods in PTEN mutation prostate cancer. Xu et al. 23 revealed that negative ACTN2 expression contributed to a better O.S. in HNSC patients, which is consistent with our present study. Therefore, ACTN2 might be an essential biomarker for predicting O.S. of HNSC, which might be employed in clinical.
Through pan-cancer analysis, we found that MYH1, MYH2, and MYH7 dysregulated in cancers, including HNSC. However, compared with HNSC, they were lower expressed in other cancers, revealing that these three genes can be considered as single biomarkers of HNSC. So far, different mutations in multiple members of the MYH gene family have been found to be associated with human hereditary diseases 24. Among them, MYH2 mutations can cause a class of skeletal muscle diseases characterized by ophthalmoplegia. MYH7 mutations can cause skeletal muscle diseases, including myosin deposition myopathy, and Distal Laing myopathy is also closely related to hypertrophic cardiomyopathy. However, the functions of MYH1, MYH2, and MYH7 in HNSC are rarely mentioned. Further study into the interaction of the MYH gene family and HHSC appears to be an intriguing research topic.
As genes highly expressed in the tumor cells are expected to affect tumor purity positively, the association between the expression of prognosis DEGs and six immune infiltrates was evaluated. We found that all the five DEGs have a significant positive correlation with CD4 + T cells and macrophages. Therefore, we speculate that genetic mutations and differential expression of ACTN2, MYH1, MYH2, MYH7, and NEB genes in HNSC cells may be important drivers of CD4 + T cell and macrophage infiltration.