Objective:To investigate the expression characteristics of phosphorylated enhancer of Zeste homolog 2(EZH2)in head and neck squamous cell carcinoma(HNSCC)and their effect on chemosensitivity.Methods:Fifty-three patients with HNSCC treated between January 2018 and March 2021 in Tianjin Medical University Cancer Institute&Hospital were selected.Expression levels of p-EZH2S21,p-STAT3Y705,HIF-1α,and Ki-67 in HNSCC tissues were analyzed by immunohistochemical staining.Western blot was used to detect p-EZH2S21 expression in HNSCC tissues and cell lines.HNSCC cell lines stably transfected with wild type(EZH2-WT)or S21 mutant EZH2(EZH2-S21A)were construc-ted.CCK8 and colony formation assays were performed to detect the effect of EZH2 and S21 phosphorylation on HNSCC cell proliferation and their sensitivity to cisplatin(DDP)and 5-fluorouracil(5-FU).Results:Elevated levels of p-EZH2S21 were observed in HNSCC tissues and positively correlated with p-STAT3Y705(P<0.05)and HIF-1α(P<0.01)levels.p-EZH2S21 level correlated positively with lymph node metastasis(P<0.000 5),T(P<0.05),N(P<0.000 1)and AJCC stages(P<0.05).In vitro experiments confirmed that EZH2 expression promoted cell prolifer-ation and attenuated chemosensitivity of HNSCC cells.Inhibition of p-EZH2S21 restored HNSCC cell sensitivity to DDP and 5-FU.Conclusions:p-EZH2S21 plays an important role in tumor progression in HNSCC,and phosphorylation at S21 is an important way for EZH2 to affect HNSCC cell proliferation and chemotherapy sensitivity.

Objective:We examined the levels of Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling in head and neck squamous cell carcinoma(HNSCC)and their influence on chemotherapy sensitization.Methods:Sixty patients with HNSCC who were treated at Tianjin Medical University Cancer Institute&Hospital,between January 2018 and December 2022,were included in the study.Levels of expressed JAK2,p-STAT3Y705,c-Myc,and Ki-67 in HNSCC tissues were evaluated using immunohistochemical staining,and correlation analysis was performed.The viability of UM-SCC1 cells treated with fedratinib,a JAK2 inhibitor,combined with cisplatin(DDP)and paclitaxel(PTX)was determined using the CCK8 assay.Western blot was performed to detect p-STAT3Y705 expression in tumor tissues and HNSCC cell lines.SCC15 and UM-SCC1 cell lines stably transfected with JAK2 or STAT3 vectors were constructed and verified.Cell activity and cell proliferation capacity were measured to evaluate the detrimental impact of STAT3 overexpression on chemotherapy with fedratinib using Western blot,CCK8,and plate cloning assays.Results:JAK2 expression in HNSCC positively correlated with p-STAT3Y705(r=0.43,P<0.000 1)and c-Myc(r=0.48,P<0.01)expression.High p-STAT3Y705 expression positively correlated with AJCC stage(P<0.000 1)and Ki-67 expression(P<0.05).High STAT3 and p-STAT3 levels were associated with poor prognosis in patients with HNSCC.In vitro,the JAK2 inhibitor fedratinib inhibited HNSCC cell proliferation and enhanced tumor cell sensitivity to DDP and PTX.JAK2 activation promotes STAT3 phosphorylation,and STAT3 overexpression reverses the effects of fedratinib on HNSCC sensitivity to chemotherapy.Conclusions:JAK2/STAT3 signaling is elev-ated in patients with HNSCC.Targeting the JAK2/STAT3 pathway is a potential method for increasing the sensitivity of HNSCC to chemotherapy.