The Study On Correlation Of Osteopontin Signal Transduction With The Occurrence And Development Of Laryngeal Squamous Cell Carcinoma

BackgroundCarcinoma of larynx is a very common malignant tumor in head and neck, and 93%-99% tissue type of this disease is laryngeal squamous cell carcinoma (LSCC). Notwithstanding primary prevention, screening, surgical treatment and radiotherapy, the long-term survival rate of laryngeal squamous cell carcinoma patients has remained substantially unchanged. With the development of tumor molecular biology, intercellular signal transduction has become popularly concentrated on biological proplem. Not only it regulates cellular growth, development, multiplocation, death and so on, but also is related to maligancies, such as laryngeal squamous cell carcinoma. Therefore, it is significant for improving effective treatment of laryngeal squamous cell carcinoma to analyze mechanism of tumor progression, invasion and cervical lymph node metastasis.Malignant tumors are characterized by dysregulated growth control and the formation of metastases. Several growth factors and cytokines play pivotal roles in the regulation of proliferation, survival, adhesion and migration of neoplastic cells. Osteopontin (OPN) is sialic-acid-rich, chemokine -like protein that plays a crucial role in determining the oncogenic potential of various cancers. OPN which is highly expressed in a wide spectrum of malignancies induces various cellular signaling events. OPN induces phosphoinositide 3-kinase (PI3K)-dependent nuclear factor kappa-B (NF-κB) activation and urokinase plasminogen activator (uPA) secretion in cancer cells. NF-kB pathway including NF-κB/P65 and NF-κB/P50 is one of the most important membrane-to-nucleus signaling mechanisms. Recent researches have shown uPA involved in tumor invasion and metastasis. Starting from protein level, the aim of this research was to investigate the correlation between OPN, NF-κB/P6, uPA expression and tumorigenesis, progression, invasion and metastasis of laryngeal squamous cell carcinoma. This study will provide new information for research on the mechanism of tumorigenesis, progression, invasion, cervical lymph node metastasis and gene therapy of laryngeal squamous cell carcinoma.ObjectiveTo investigate the correlation between the signal pathway induced by OPN and occurrence, development, clinicopathologic tumor features of laryngeal squamous cell carcinoma. This study will provide new information for research on the mechanism of invasion and metastasis and therapeutic targets of laryngeal squamous cell carcinoma.MethodsThe expression of OPN, NF-κB/P65 and uPA was confirmed by immuno-histochemical method (Streptavidin/Peroxidase, S-P) in 57 cases of laryngeal squamous cell carcinoma (experimental group) and 10 cases of adjacent noncarcinoma tissue (control group). To respectively compare the three protein expression differences between the experimental group and the control group, and compare respectively the relationships between the protein expression and the major clinic indexes, and to analyze the correlation between OPN and NF-κB/P65, OPN and uPA, NF-κB/P65 and uPA. Statistical analysis was done by the SPSS software program version 11.0. Results[1] The expression of OPN, NF-κB/P65 and uPA was higher in the laryngeal squamous cell carcinoma than that of it in the adjacent noncarcinoma tissue, and the difference between them had statistical significance (P<0.05). Positive expression rate of OPN, NF-κB/P65 and uPA in laryngeal squamous cell carcinoma was respectively 59.6% (34/57), 61.4 % (35/57) and 70.2% (40/57).[2] Positive expression of OPN in G₂/G₃(79.2%) was higher than that of it in G₁ (45.5%), and the difference between them had statistical significance (P<0.05); positive expression of OPN in T₃/T₄(76.0%) was higher than that of it in T₁/T₂(46.9%), and the difference between them had statistical significance (P<0.05); there was no significant differences among positive expression of NF-κB/P65 and uPA in tumor stage and the degree of differentiation (P>0.05).[3] Positive expression of OPN, NF-κB/P65, uPA in TNM 3-4 stage was much higher than that of it in TNM 1-2 stage, and the difference between them had statistical significance (P<0.05); cases of lymph node metastasis had higher expression of OPN, NF-κB/P65, uPA than cases without lymph node metastasis, and the difference between them had statistical significance (P<0.05).[4] The expression of OPN and NF-κB/P65, NF-κB/P65 and uPA, uPA and OPN was well correlated separately (P<0.05).Conclusion[1] The expression of OPN, NF-kB/P65 and uPA was higher in the laryngeal squamous cell carcinoma than that of it in the adjacent noncarcinoma tissue, which indicated that they took part in the occurrence and development of laryngeal squamous cell carcinoma; moreover, positive expression of OPN in G₂/G₃ was higher than that of it in G₁, and positive expression of OPN in T3/T4 was higher than that of it in T₁/T₂.[2] Positive expression of OPN, NF-κB/P65, uPA in TNM 3-4 stage was much higher than that of it in TNM 1-2 stage, and cases of lymph node metastasis had higher expression of OPN, NF-κB/P65 and uPA than cases without lymph node metastasis, which indicated that they played important role in the invasiveness and metastasis of laryngeal squamous cell carcinoma.[3] The expression of OPN and NF-κB/P65, NF-κB/P65 and uPA, uPA and OPN was well correlated separately, which indicated that activation of NF-κB signal pathway induced by OPN took part in the occurrence and development of laryngeal squamous cell carcinoma.