The Biological Significance And The Related Molecular Mechanism Of Survivin Protein And MRNA Expression In Lung Cancer Progression Tissue Microarray

Objective:We intended to detect the expressions of Survivin, PTEN, bFGF protein and Survivin mRNA in lung cancer progression tissue microarray and to discuss their roles in lung cancer genesis and progress and analyze the probable molecular mechanism. With these results, we wanted to put our discoveries into the clinicopathological diagnosis, prognosis evaluation and gene therapy. Material and Method:We used SP immunohistochemistry method to detect the expressions of Survivin, PTEN and bFGF protein, FISH method to detect the expression of Survivin mRNA in tissue microarray with 270 cores, in which there were 89 cases of primary lung cancer, 12 cases of lymph node metastasis of lung cancer, 12 cases of precancerous lesion and 10 cases of normal lung tissue. All data were processed by SPSS version 11.0 analysis software. Result:1.The tissue microarray block was exquisite and had no splits.269 cores were arranged on the block and slides except 1 core shifted a little. There were no losing and distort of the tissue cores after staining. They were fit for research. 2. Survivin protein were respectively detected in 0 (0/10) ,41.7% (5/12) , 57.3% (51/89) and 75.0% (9/12) of normal lung tissue, precancerous lesion, primary lungcancer and lymph node metastasis of lung cancer; the positive rate of Survivin protein in primary lung cancer and precancerous lesion were significantly higher than that of normal lung tissue(p<0.05).3. The positive rate of Survivin protein in different histological types of primary lung cancer were various. They were: adenocarcinoma 54.3% ( 19/35) , squamous cell lung cancer 51.5% (17/33) , SCLC 83.3% (10/12) , LCLC 55.6% (5/9) . There were no significant difference between them (p>0.05) .4. In primary lung cancer, the expression degrees of Survivin protein had significantly positive correlation with the differentiation and clinical stages of lung cancer(p<0. 05 ). The positive rate of Survivin protein was significantly higher in the group with lymph node metastasis than that without lymph node metastasis (p<0. 05); it was higher in the group of III+IV stage than in I +11 stage (p<0. 05) .5. PTEN protein were respectively detected in 90.0% (9/10) , 66.7% (8/12) , 44.9% (40/89) and 25.0% (3/12) of normal lung tissue, precancerous lesion, primary lungcancer and lymph node metastasis of lung cancer; the positive rate of PTEN protein in primary lung cancer was significantly lower than that of normal lung tissue(p<0.05).6. The positive rate of PTEN protein in different histological types of primary lung cancer were various. They were: adenocarcinoma 54.3% (19/35), squamous cell lung cancer 42.4% (14/33) , SCLC 33.3% (4/12) , LCLC 33.3% (3/9) .There were no significant difference between them (p>0.05 ) .7. The positive rate of PTEN protein was significantly related to differentiation degrees, lymph node metastasis and clinical stages. It was higher in the group of high-middle differentiation than that of low-un differentiation; it was higher in the group without lymph node metastasis than that with lymph node metastasis (p<0. 05); it was higher in the group of I +11 stage than that in III+IV stage ( p<0. 05) .8. bFGF protein were respectively detected in 0(0/10), 25.0%(3/12), 66.3%(59/89) and 83.3% (10/12) of normal lung tissue, precancerous lesion, primary lung cancer and lymph node metastasis of lung cancer; the positive rate of bFGF protein inprimary lung cancer was significantly higher than that of normal lung tissue and precancerous lesion (p<0.05).9. The positive rate of bFGF protein in different histological types of primary lung cancer were various. They were: adenocarcinoma 68. 6% (24/35), squamous cell lung cancer 60. 6% (20/33) , SCLC 66. 7% (8/12) , LCLC 77. 8% (7/9) . There were no significant difference between them (p>0.05) .10. The positive rate of bFGF protein was significantly related to lymph node metastasis and clinical stages. It was higher in the group with lymph node metastasis than that without lymph node metastasis (p<0. 05) ; it was higher in the group of 111+ IV stage than in I + II stage (p<0. 05) .11. There were no significant difference between the groups of different gross types, ages and sexes (p>0.05) .12. There was significantly negative correlation between Survivin and PTEN (rs= -0.479, p<0.05) , there was significantly positive correlation between Survivin and bFGF (rs=0.628, p<0.05)o13. Survivin mRNA were respectively detected in 0 (0/10) , 41.7% (5/12) , 69.7% (62/89) and 91.7% (11/12) of normal lung tissue, precancerous lesion, primary lungcancer and lymph node metastasis of lung cancer; the positive rate of Survivin mRNA in primary lung cancer and precancerous lesion were significantly higher than that of normal lung tissue(p<0.05).14. The positive rate of Survivin mRNA in different histological types of primary lung cancer were various. They were: adenocarcinoma 68.6% (24/35), squamous cell lung cancer 60.6% ( 20/33) , SCLC 91.7% (11 /12 ) , LCLC 77.7% (7/9 ) . There were no significant difference between them (p>0.05) .15. The positive rate of Survivin mRNA was significantly related to differentiation degrees, lymph node metastasis and clinical stages. It was higher in the group of low-un differentiation than that of high-middle differentiation; it was higher in the group with lymph node metastasis than that without lymph node metastasis (p<0. 05); it was higher in the group of III+IV stage than in I +11 stage (p<0. 05) .16. The expression of Survivin mRNA and Survivin protein had significantly positivecorrelation (rs=0.842, p<0.05) .Conclusions:1. The positive rate of Survivin protein was higher in primary lung cancer and precancerous lesion than that in normal lung tissue, which suggested that Survivin promote the genesis and progress of lung cancer, it played an important role from the early stage of lung cancer genesis; Survivin may have important value in early stage diagnosis of lung cancer, may become a new target for gene therapy.2. In primary lung cancer, the expression degrees of Survivin protein had significantly positive correlation with the differentiation and clinical stages of lung cancer. The positive rate of Survivin protein was significantly higher in the group with lymph node metastasis than that without lymph node metastasis; it was higher in the group of III + IV stage than in I + II stage.These suggested that Survivin can promote infiltration and metastasis of lung cancer; it was related to the progression and malignant biological behavior; it can be a reference in prognosis evaluation.3. The positive rate of PTEN protein was lower in primary lung cancer than that in normal lung tissue, which proved that PTEN was a tumor inhibitor, which played an important role on inhibiting lung cancer genesis and progress; the deletion of it can promote the genesis and progress of lung cancer.4. The positive rate of PTEN protein was significantly related to differentiation degrees, lymph node metastasis and clinical stages, which suggested that the deletion of PTEN can promote the malignant transformation and progression; PTEN may play a role on the inhibition of tumor infiltration and metastasis; it can be a reference in prognosis evaluation.5. The positive rate of bFGF protein was higher in primary lung cancer than that in normal lung tissue and precancerous lesion, which suggested that bFGF promote the genesis and progress of lung cancer.6. The positive rate of bFGF protein was significantly related to lymph node metastasis and clinical stages, which suggested that bFGF can play along withinfiltration and metastasis of tumor through promoting tumor proliferation and vascularization; it can be a reference marker of prognosis evaluation.7. Survivin and PTEN had negative correlation, which suggested that PTEN can inhibit lung cancer genesis and progress; it can down-regulate the expression of Survivin, its deletion can up-regulate Survivin and promote tumor genesis and progress. Survivin and bFGF had positive correlation, which suggested that bFGF can up-regulate Survivin and promote the proliferation, infiltration and metastasis. The study of their relationship can reveal the mechanism related to lung cancer genesis and progress and provide theoretical evidence for gene therapy.8. The positive rate of Survivin mRNA was higher in primary lung cancer and precancerous lesion than that in normal lung tissue, which suggested that Survivin promote the genesis and progress of lung cancer, it played an important role from the early stage of lung cancer genesis; Survivin may have important value in early stage diagnosis of lung cancer, may become a new target for gene therapy.9. The positive rate of Survivin mRNA was higher in the group of low-un differentiation than that of high-middle differentiation; it was higher in the group with lymph node metastasis than that without lymph node metastasis; it was higher in the group of III + IV stage than in I + II stage. These suggested that Survivin can promote infiltration and metastasis of lung cancer ;it was related to the progression and malignant biological behavior; it can be a reference in prognosis evaluation.10. There was positive correlation between the expressions of Survivin mRNA and protein; their expressions in different groups and between different clinicopathological parameters were similar, which proved that mRNA can guide the protein synthesis, so that the increase of Survivin mRNA can enhance the Survivin protein synthesis.11. The positive rate of Survivin mRNA was a little higher or equal with that of Survivin protein which suggested that FISH has good sensitivity and stability; it has high detectable rate of mRNA; it will be widely used in molecular pathology.