Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck ; Carcinogenesis/genetics* ; Cell Transformation, Neoplastic ; Wnt Signaling Pathway ; Disease Models, Animal ; Head and Neck Neoplasms/genetics* ; Wnt Proteins ; Frizzled Receptors/genetics* ; Janus Kinase 1 ; STAT3 Transcription Factor

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

ObjectiveTo investigate the expression and clinical significance of programmed death-1 (PD-1) and T-cell immunoglobulin- and mucin domain-3-containing molecule 3 (TIM-3) in hepatocellular carcinoma (HCC). MethodsThe paraffin blocks of HCC tissue and adjacent tissue (＞1 cm from the tumor margin) were collected from 46 patients with HCC who underwent surgical treatment in No. 900 Hospital of The Joint Service and Security Force of The Chinese People’s Liberation Army from January 2013 to December 2015. Immunohistochemistry was used to measure the expression of PD-1 and TIM-3, and their association with clinicopathological features and prognosis was analyzed. The Wilcoxon test was used for comparison of paired ranked data, and a Spearman correlation analysis was used to investigate the correlation between ranked data; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison of survival rates between groups; the Cox regression model was used to perform a multivariate analysis. ResultsThe expression levels of PD-1 and TIM-3 in HCC tissue were higher than those in adjacent tissue (both P＜0.05). PD-1 was mainly localized in lymphocytes and TIM-3 was mainly localized in tumor-associated macrophages. The expression of PD-1 was positively correlated with that of TIM-3 in HCC tissue (rs=0.397, P=0.006). The expression level of PD-1 in HCC tissue was associated with tumor size (rs=0.480, P=0.001), portal vein tumor thrombus (rs=0.307, P=0.038), and TNM stage (rs=0.534, P＜0.001), and the expression level of TIM-3 was associated with portal vein tumor thrombus (rs=0.301, P=0.042), degree of pathological differentiation (rs=0356, P=0.015), and TNM stage (rs=0.416, P=0.004). For the patients with HCC, the 1-, 3-, and 5-year overall survival rates were 89.1%, 56.5%, and 34.4%, respectively, and the 1-, 3-, and 5-year disease-free survival rates were 52.2%, 21.7%, and 10.9%, respectively. The multivariate analysis showed that degree of pathological differentiation (hazard ratio ［HR］=4.723, 95% confidence interval ［CI］: 1.618-7.684, P=0.001), tumor size (HR=3.234, 95%CI: 1.327-7.883, P=0.010), TNM stage (HR=3.254, 95%CI: 1.076-9.835, P=0.037), and expression level of TIM-3 (HR=0.572, 95%CI: 0.329-0.995, P=0048) were independent prognostic factors for the overall survival of HCC patients, and degree of pathological differentiation (HR=2.945, 95%CI: 1.527-5.682, P=0.001) and TNM stage (HR=2.074, 95%CI: 1.259-9.793, P=0.016) were independent prognostic factors for the disease-free survival of HCC patients. ConclusionHigh expression levels of both PD-1 and TIM-3 are observed in HCC tissue, and PD-1 and TIM-3 may be involved in the progression and poor prognosis of HCC patients.