Effect And Significances Of TGF-β1/SMAD4 Signalpathway In Laryngeal Carcinoma

ObjectiveTo explore the effect of TGF-β1/Smad4 signaling system in Laryngeal squamous cell carcinoma by investigating the expression of Transforming growth factor-β1(TGF-β1), Transforming growth factor-βreceptorII (TβRII) and Smad4 in human laryngeal squamous cell carcinoma(LSCC) and normal laryngeal mucosa. It would provide the basis for judging to stage of LSCC's invasion and predicting the prognosis, finding new methods of therapy.MethodsTissue of LSCC were obtained from 44 patients who underwent surgery as for Experimental group, Tumors were graded according to histology, well-differentiated LSCC, 20 samples; moderate differentiated LSCC, 15 samples; poorly differentiated LSCC, 9 samples; with regional lymph node invasion group (27 cases) and without regional lymph node invasion group (17 cases). Clinical stage according the criterion of UICC 2002, GradeⅠ-Ⅱ, 19 samples; GradeⅢ-Ⅳ, 25 samples. Tissues of normal laryngeal mucosa were obtained from 14 as for control group. Immunohistochemical staining of the sections TGF-β1, Smad4 protein was assessed according to both the distribution (the percentage of positive cells) and the intensity of staining. The results were analyzed statistically, and relationship with LSCC progress and metastasis was analyzed.ResultsTGF-β1 and smad4 positive staining was observed in cytoplasm, TβRII positive staining was observed in cell membrane. The expression rate of TGF-β1 in LSCC group was 68.2%, which has a significant difference from normal laryngeal mucos group (30.0%, P < 0.05). In LSCC group, the positive expression rate of TβRII and Smad4 was 40.9%, 34.1% respectively; while 80.0%, 80.0% respectively in normal laryngeal mucosa group, there were statistical significance between LSCC group and laryngeal mucosa group (P < 0.05). The expression of TGF-β1 in LSCC tissue was associated with clinical stage and lymph node metastasis (P < 0.05), and no obvious relationship with the extent of tissue differentiation (P > 0.05). The expression of TβRII was only associated with clinical, no relationship with lymph node metastasis and tissue differentiation (P > 0.05). The expression of smad4 in LSCC tissue was associated with clinical stage, lymph node metastasis and tissue differentiation (P < 0.05). A negative correlation was observed between the expression of TGF-β1 and that of TβRII (P < 0.05). The same was observed between the expression of TGF-β1 and that of smad4 (P < 0.05). A positive correlation was observed between the expression of smad4 and that of TβRII (P < 0.05).ConclusionAbnormal TGF-β1/smad4 signaling system is involved in occurrence and progression of LSCC. The overexpression of TGF-β1 is associated with occurrence and development of LSCC. Low expression of TβRII is related to clinical stage. Decreased expression of smad4 may accelerate the invasion or metastasis of LSCC.