Expression Of DKK1, SFRP4 And Wnt1 In Laryngeal Squamous Cell Carcinoma And Its Significance

Objective: Laryngeal cancer is the most common malignancy of the head and neck region, with a significantly increased incidence in recent years. 93%-99% of laryngeal cancer falls into the category of laryngeal squamous cell carcinoma(LSCC), occurrence, development, invasion and metastasis of which is a process involving multiple genes, multiple stages and multiple factors. Therefore, it is of great significance to study pathogenesis and development of laryngeal cancer in terms of clinically effective prevention and treatment. Currently, tumor signaling pathway more level targets for cancer treatment has become a hot spot in research of molecular tumor biology. Development of drugs targeting different gene targets and genes with high specificity as well as molecular diagnosis of tumors are new research areas for diagnosis and treatment of cancer. Thus, in the present study, immunohistochemistry method was used to detect expression of DKK1, SFRP4 and Wnt1 in LSCC tissues and normal laryngeal mucosa, to analyze their expression difference and correlation of their expression to patient’s age, clinical stage, lymph node metastasis, pathological differentiation and smoking. Furthermore, role of DKK1, SFRP4 and Wnt1 in the Wnt/β-catenin signal transduction pathway and its significance were also explored.Methods:Sixty-four cases of laryngeal cancer tissues and 30 cases of normal laryngeal mucosa were taken from patients diagnosed with laryngeal cancer in the ENT of head and neck surgery in Fourth Hospital of Hebei Medical University from April 2010 to September 2014. All laryngeal carcinoma tissues were pathologically confirmed to be laryngeal squamous cell carcinoma(LSCC), and patients enrolled in this study had no preoperative radiotherapy and chemotherapy. Immunohistochemistry method(SP method) was used to detect expression of DKK1, SFRP4 and Wnt1 in 64 cases of LSCC tissues and 30 cases of normal laryngeal mucosa. SPSS19.0 statistical software was used to analyze and compare all the experimental data, coupled with IPP and clinical and pathological features of the patients.Results:1 Expression of DKK1 in LSCC tissues and normal laryngeal mucosa.DKK1 protein expression was different in LSCC tissues and normal laryngeal mucosa. DKK1 protein expression in LSCC tissues(32.8%) was lower than that in the group with normal laryngeal mucosa(66.7%), and the difference was statistically significant(P<0.01).2 Expression of SFRP4 in LSCC tissues and normal laryngeal mucosaSFRP4 protein expression was different in LSCC tissues and normal laryngeal mucosa. SFRP4 protein expression in LSCC tissues(62.5%) was higher than that in the group with normal laryngeal mucosa(40.0%), and the difference was statistically significant(P<0.05).3 Wnt1 expression in LSCC and normal laryngeal mucosaWnt1 protein expression was different in both LSCC tissues and normal laryngeal mucosa. Wnt1 protein expression in LSCC tissues(65.6%) was higher than that in the group with normal laryngeal mucosa(30.0%), and there was statistically significant difference(P<0.01).4 The relationship between DKK1 expression and clinicopathological parameters of LSCCDKK1 protein positive expression of LSCC tissues was lower in the group with lymph node metastasis(20.6%) compared with the group without lymph node metastasis(46.7%)(P<0.05). Expression in stage Ⅲ and Ⅳ(according to UICC) group(17.9%) was lower than that in stage I and Ⅱgroup(44.4%)(P<0.05). Expression in the group with poorly differentiated LSCC(15.0%) was lower, compared with the group with moderate-high differentiated LSCC(40.9%)(P<0.05).No significant difference was observed in DKK1 protein expression(P> 0.05, P> 0.05) in groups with different ages and smoking.5 The relationship between SFRP4 and clinicopathological parameters of LSCCSFRP4 protein positive expression of LSCC tissues in the group with lymph node metastasis(76.5%) was higher than that in the group without lymph node metastasis(46.7%)(P<0.05). Expression in stage Ⅲ and Ⅳ(according to UICC) group(78.6%) was higher than that in stage I and Ⅱgroup(50.0%)(P<0.05). Expression in the group with poorly differentiated LSCC(85.0%) was higher than that in the group with moderate-high differentiated LSCC(52.3%)(P<0.05).No significant difference(P>0.05, P>0.05) was observed SFRP4 protein expression in groups with different age and smoking.6 The relationship between Wnt1 and clinicopathological parameters of LSCCWnt1 protein positive expression in LSCC tissues was higher in the group with lymph node metastasis(79.4%) compared with that in the group without lymph node metastasis(50.0%)(P<0.05). The expression in stage Ⅲand Ⅳ(according to UICC) group(82.1%) was higher than that in stage I and Ⅱgroup(52.8%)(P<0.05). The expression in the group with poorly differentiated LSCC(90.0%) was higher, compared with that in the group with moderate-high differentiated LSCC(54.4%)(P<0.05).Wnt1 protein expression was not significantly different(P>0.05, P>0.05) in groups with different ages and smoking.7 The mutual relationship among expression of DKK1, SFRP4 and Wnt1 in LSCC tissuesExpression of DKK1 in LSCC tissues had a significantly negative correlation with expression of Wnt1(r=-0.335, P<0.01). Expression of SFRP4 and Wnt1 in LSCC tissues had a significant positive correlation(r=0.391, P<0.01). Expression of DKK1 in LSCC tissues was negatively correlated with SFRP4(r=-0.352, P<0.01).Conclusions:1 DKK1 expression in the group with LSCC tissues was lower than that in the group with normal laryngeal mucosa; SFRP4 expression in LSCC tissues was higher than that in the normal laryngeal mucosa; Wnt1 expression in LSCC was higher than that in normal laryngeal mucosa, and the difference were statistically significant.2 Expression of DKK1, SFRP4 and Wnt1 in LSCC was statistically significant in groups with lymph node metastasis, UICC staging and pathological differentiation, but was not significantly different in groups with different ages and smoking.3 Low expression of DKK1 as well as high expression SFRP4 and Wnt1 played an important role in the pathogenesis of SLCC, as a predictive factor of metastasis and prognosis of LSCC.4 DKK1 expression in LSCC tissues showed a significant negative correlation with SFRP4 and Wnt1, respectively. SFRP4 expression was positively correlated with Wnt1 expression.5 DKK1 might play a role as an inhibiting factor in the pathogenesis and development of LSCC. But, SFRP4 and Wnt1 may have a synergistic effect, and their high expression may play an important role in the pathogenesis and development of LSCC.