ABSTRACT
Background: Plasma protein patterns differ between cancer patients and healthy donors. This study aimed to examine the plasma levels of several cytokines and immunological checkpoint proteins between patients with oral and oropharyngeal cancer and healthy donors. Materials and methods: Plasma samples from healthy donors, oral cancer patients, and oropharyngeal cancer patients were analyzed using the Human Th Cytokine Panel 13-plex (IL-2, 4, 5, 6, 9, 10, 13, 17A, 17F, 21, 22, IFN-γ, and TNF-α) and Human Immune Checkpoint Panel1 12-plex [sCD25 (IL-2Ra), 4-1BB, sCD27, B7.2 (CD86), Free Active TGF-ß1, CTLA-4, PD-L1, PD-L2, PD-1, Tim-3, LAG-3, and Galectin-9]. The plasma 4-1BB levels were verified by Western blot method. In addition, the study of the receive operating curve (ROC) yielded the calculation of a number of diagnostically significant indicators. Results: Significantly increased levels of IL-6, 4-1BB, PDL-1, PD-1, and CTLA-4 and decreased levels of IL-13 and sCD27 were observed in cancer patients compared with healthy donors. These levels were highly significant, particularly for cancer patients in stage IV. Validation by Western blot revealed that cancer patients had higher plasma levels of 4-1BB than healthy donors (p < 0.05), and ROC curve analysis revealed that plasma 4-1BB had the highest cancer detection capability. Intriguingly, plasma levels of 4-1BB were significantly positively correlated with PDL-1 and PD-1 levels (p < 0.0001). Conclusion: This data provided descriptive knowledge of oral and oropharyngeal cancer immunity at a fundamental level. Additional research should concentrate on the significantly different factors, especially 4-1BB, PDL-1, and PD-1, which may contribute to the development of novel alternative diagnostic tools or therapies for patients with oral and oropharyngeal cancer.
ABSTRACT
The endogenous DNA damage triggering an aging progression in the elderly is prevented in the youth, probably by naturally occurring DNA gaps. Decreased DNA gaps are found during chronological aging in yeast. So we named the gaps "Youth-DNA-GAPs." The gaps are hidden by histone deacetylation to prevent DNA break response and were also reduced in cells lacking either the high-mobility group box (HMGB) or the NAD-dependent histone deacetylase, SIR2. A reduction in DNA gaps results in shearing DNA strands and decreasing cell viability. Here, we show the roles of DNA gaps in genomic stability and aging prevention in mammals. The number of Youth-DNA-GAPs were low in senescent cells, two aging rat models, and the elderly. Box A domain of HMGB1 acts as molecular scissors in producing DNA gaps. Increased gaps consolidated DNA durability, leading to DNA protection and improved aging features in senescent cells and two aging rat models similar to those of young organisms. Like the naturally occurring Youth-DNA-GAPs, Box A-produced DNA gaps avoided DNA double-strand break response by histone deacetylation and SIRT1, a Sir2 homolog. In conclusion, Youth-DNA-GAPs are a biomarker determining the DNA aging stage (young/old). Box A-produced DNA gaps ultimately reverse aging features. Therefore, DNA gap formation is a potential strategy to monitor and treat aging-associated diseases.
