Study On The Biological Significance Of Expression Of Stat3, Bcl-2 And VEGF In Lung Cancer Tissue Microarray And Its Relative Molecular Mechanism

Objective:To make clear the roles which Stat3, bcl-2 and VEGF played in occurrence, development of lung cancer and probable molecular mechanism of it, we intended to detect the expression of them in a lung cancer tissue microarray and analyzed the relationship between them. We hope to supply a theoretical evidence for diagnosis, tumor therapy and judgment of prognosis.Material and Methods:We applied tissue microarray technique and SP immunohistochemical method to detect Stat3, bcl-2 and VEGF protein expressions and analyzed their relationship with each other in a lung cancer tissue microarray containing normal lung tissue specimen, precancerous diseases, cancer specimen and metastasis specimen. All data were processed by SPSS version 11.5 analysis software.Results:1. The result of factured TMA: The character of our recipient block was exquisite and had no splits. The chip cores were arranged orderly and clearly in the block. The chip cores had no shift and distort and obviously rugate in slides when they cut from block. They were answered for the request of research.2. Stat3, bcl-2 and VEGF proteins were respectively detected in 65.17%, 77.53 % and 79.77% of all the 89 lung cancer tissues, which were higher than those of controlgroup, and the differences were significant (P<0.05).3. There was significant difference between the expression of Stat3 in peripheral type and in central type of lung cancer. The central type (83.33%) was much higher than the peripheral type (55.93%) (P <0.05).4. The expressions of Stat3 in different histological types of lung cancers were various. Those were: SCLC (91.67%)>squamous cell lung carcinoma (69.70%) >adenocarcinoma (57.14%) >LCLC (44.44%);SCLC (91.67%) >NSCLC (61.04%), and the differences were not significant (P >0.05).5. The expression of Stat3 in different histological grades and clinical stages were various. Low grade (80.55%)>high-middle grade (54.71%), HI+IV (78.79%) >I+II (57.14%), and the differences were significant (P <0.05). The expression of Stat3 in lung cancer was associated with lymph node metastasis (P <0.05).6. There was significant difference between the expression of VEGF in peripheral type and in central type of lung cancer. The positive rates of peripheral type and central type were respectively 84.74 % and 63.33%( P <0.05). The expressions of Stat3 in different histological types of lung cancers were various. Those were: SCLC (83.33%)>adenocarcinoma (78.79%) >squamous cell lung carcinoma (77.14%) >LCLC (66.67%);SCLC (83.33%) >NSCLC (76.62%), and the differences were not significant (P >0.05).7. The expression of VEGF was associated with the histological grades, clinical stages and with or without lymph node metastasis. Low grade (91.66%)>high-middle grade (67.92%), III+IV (90.91 %)>I+II (69.64%), with lymph nodemetastasis (91.67%) >without lymph node metastasis (60.98%). The differences were significant (P <0.05).8. The positive rate of bcl-2 was 20% in 10 cases of normal tissues and 33.33% inprecancerous tissues, 70.73 % in primary lung cancers, and the difference among them was significant (.P<0.05) . Its expression was not related to the histological types and grades. SCLC (83.33%)>squamous cell lung carcinoma (81.82%)> adenocarcinoma (80.00%) >LCLC (77.78%);Low grade (80.00%) > middle grade (72.73%)>high grade (45.00%). But there were not significant difference among them (F>0.05).9. The expression of bcl-2 was very different with different clinical stages and lymph node metastasis. III+IV (90.91%)>I+II (71.43%), with lymph node metastasis (89.58%) >without lymph node metastasis (68.29%) (P<0.05).10. No significant differences were detected between these three proteins expressions of different sexes and ages (P >0.05).11. There was significantly positive association between stat3 expression and VEGF expression (/y=0.311, i>=0.000).The expression of Stat3 was positive related to the bcl-2 expression (r*=0.299, P=0.001).Conclusion:1. TMA, as a high and new technique, could be used on science research and clinicopathological diagnosis. It can save time and reagent. Low rate of experimental error is its important character. TMA will be a useful weapon for pathological scientists in science research.2. The expression of Stat3 was higher in premalignant lesions and lung cancer samples, in normal lung tissues its expression was 0, which suggested it involved in carcinogenesis of human lung cancer. We detected that the expression was much higher with lymph node metastasis. It proved that Stat3 protein had a relationship with metastasis function in lung cancer. The Stat3 expression correlated with gross types of lung cancer, and preferred to expression in central type. Our study providedtheoretical basis to the individual therapy of lung cancer. There were some differences among the Stat3 expression of different types of lung cancer. SCLC>squamous cell lung carcinoma>adenocarcinoma>LCLC. Though the differences were not significant, it still could prove the mechanism in different types were various.3. The expressions of Stat3 in primary lung cancer gradually higher following the decrease of tumor cell differentiated degree and clinical stages. This suggested Stat3 played an important role in proliferation of tumor cells. Detected the marker will important to estimate cancer progression and guide the clinical therapy of lung cancer.4. The expression of VEGF was increased in primary lung cancer and premalignant lesions, and it was much stronger in lower histological and higher clinical stage. Our experiment proved it was significantly associated with the expression of Stat3, which suggested there maybe exist cooperation between them. While Stat3 was activated, it could promote the expression of VEGF and induce tumor angiogenesis. It was morphological bases for tumor growth and metastasis.5. Normal lung tissues had positive expressions of bcl-2, but it was overexpressed in lung cancer samples .Its expression could depress the apoptosis of tumor cells and it played an important role in tumorigenesis of human lung cancer. In our research, there were significant correlation between Stat3 and bcl-2, which showed Stat3 could up-regulate the expression of bcl-2 and through the downstream pathway to influence the growth, infiltration of lung cancer.6. There was no significant relationship between bcl-2 and VEGF, which suggested they might have different mechanism on depressing the apoptosis of tumor cells and inducing tumor angiogenesis. They played different roles in carciongenesis andgrowth of human lung cancer.