The Relation Between Several Molecular Markers And Biological Trait, Efficacy In No Small Cell Lung Cancer

Background:Recently, the incidence and mortality of lung cancer in whole world continue to increase and be highest in all of malignancy, about 80% of them is no small cell lung cancer(NSCLC). And 50% of patients given the diagnosis of NSCLC belong to advanced disease. They usually have several metastasis without discovered by routine medical examination . Thus, the NSCLC relapse quickly after operation. Now, chemotherapy plays a key role in treatment of advanced NSCLC. But, efficacy of chemotherapy is very limited . The phenomenon of drug resistant in NSCLC is very common. There are some markers ( such as MDR , CEA, NSE, CYFRA21-1 and so on)which are difficult of truly, rounds timely responding biological trait and efficacy of NSCLC. So it is anxious to find more sensitive markers with estimating early metastasis and efficacy to make up marker group.Objective:We select a series of markers which reflect proliferation, differentiation, metastasis,apoptosis, angiogenesis of tumor by examining in tumor tissues or peripheral blood and Summary data of follow-up visiting. Then, we want to clarify inherence relation and correlative clinical signification of lung cancer markers which are mutual relevancy and could be important clinical signification.Methods:The study is comprised of there parts.Part I : To examine tumor tissue. Such as protein of Survivin, VEGF, C0X-2,C-erbB2 by immunohistochemistry. Part II : Anteroposterior changes of treatment in peripheral blood of patients with advanced NSCLC. Such as circulating endothelial cells by flow cytometry;Survivin by RT-PCR , real-time PCR;CYFRA21-land CEA and NSE by electrochemistry illurainant method. Part III: Survival analysis with 20 months of follow-up .Results1. Detection in turmor tissue: 30 of 37 NSCLC patients have tumor tissue specimen.(1) Masculine rate of protein with Survivin, C-erbB2 ,C0X2, VEGF were 60%, 46. 67%, 56.67%, 63. 33%respectively. Positive correlation was found between Survivin, C0X2 and VEGF by Spearman correlation analyses . The identical relation was found between Survivin and C~erbB2 too.No correlation was found between C~erbB2 and COX2 or VEGF. Correlation coefficients which belonged to Survivin, C-erbB2 , C0X2, VEGF were 0. 572, 0.647, 0.754, 0.735 (P >0. 05) respectively.(2) No variance was found in masculine rate of protein with Survivin, C-erbB2 , VEGF of different' sex , age, patho-type groups. While, the variance was found in masculine rate of protein with Survivin, C-erbB2 , VEGF with different diameter of primarily tumor( ^3cm and<3cm), metaptosis of lymph node or distant place. No variance was found in masculine rate of COX-2 with patients'sex , age, patho-type , diameter of primarily tumor , metaptosis of lymph node or distant place groups.2. Detection in in peripheral blood:(l)No variance was found in the number of CECs before treatment or A CECs(=CECs before treatment -CECs after treatment) of different sex n ageN patho-type , diameter of primarily tumor > metaptosis of lymph node or distant place groups. Apparente variance was found in A CECs and efficacy. Patients in benefit group had a little decrease in number of ACECs while patients out of benefit had a tendency of increase in number of ACECs (p=0. 000).(2) 24 out of 37 patients expressed Survivin mRNA, masculine rate of Survivin mRNA is 64. 86%. No variance was found in the level of Survivin mRNA before treatment or A Survivin mRNA (=Survivin mRNA before treatment - Survivin mRNA after treatment) of different sex , age, patho-type groups(all P>0. 05). While, the variance was found in the level of Survivin mRNA before treatment or A Survivin mRNA with different diameter of primarily tumor > metaptosis of lymph node or distant place groups (all PCO. 05). Patients in benefit had a little decrease in number of A Survivin mRNA while patients out of benefit had a tendency of increase in number of A Survivin mRNA (p=0.000) .(3) Positive correlation was found between the level of Survivin mRNA in peripheral blood of NSCLC before operation and it's protein in tumor tissues. No correlation was found between Survivin mRNA in peripheral blood of NSCLC before operation and C-erbB2 ? VEGF^ C0X2 protein in tumor tissues. Between the level of CECs before operation and Survivin > C~erbB2 , C0X2, VEGF protein in tumor tissues had no correlation .(4) No variance was found in masculine rate of Lung cancer marks(CEA, CyFRA21-l, NSE) in peripheral blood with different age > sex groups;while the variance was found in masculine rate of them in different diameterof primarily tumor ^ metaptosis of lymph node or distant place groups. Masculine rate of CEA in squanrlung caner or lung adenic caner were 39. 1%, 92. 9% respectively. The different of them was singif icant. Masculine rate of CYFRA21-1 in lung squamosal caner or lung adenic caner were 73.9%^ 35.7% respectively.The different of them was singificant. (5) It was found a strong correlation between efficacy and A CECS^ A Survivin mRNAx ACYFRA21-1 in lung squanrcaner. There is positive correlation between ACECS and ASurvivinmRNA or ACYFRA21-1 (correlation coefficient is 0. 54^ 0. 523, all P<0. 05) .while no correlation between ASurvivin mRNA and ACYFRA21-1 in lung squamosal caner (P>0.05) . It was found a strong correlation between efficacy and A CECS> A Survivin mRNA> A CEA in lung adeno-caner. There were positive mutual correlation between A CECs ^ A Survivin mRNA and ACEA in lung adenic caner (correlation coefficient was -0.54^ 0.523, all P<0.05) .3. Influential factor of long-term survival:The conspicuous variance was found in survival time of different therapy>. A CECs> TTP groups by Kaplan-Meier survival analysis . The former survival rate of 1 year was high between chemotherapy plus Endostatin group and simple chemotherapy group or 5=100 days and <100 days of TTP group or 2?2 and <2 of ACECs group. Conclusions1. Co-positive correlation was found between protein of Survivin COX-2 and VEGF or protein of Survivin and C-erbB2 in NSCLC tissues. It showed that these marks conjointly play considerable key roles with NSCLC.2. A strong correlation was found between protein of Survivn ^ C-erbB2 .. VEGF in tissues ^ SurvivinmRNA^ CEA^ NSE, CYFRA21-1 in peripheral bloodof NSCLC and patients' TNM-staging. There was no correlation between COX-2 protein in tumor tissues^ CECs in peripheral blood and patients' TNM-staging. These datas demonstrated that the former marks could be forecast metastasis of distant place and burden of turmor, the latter markers had no such effect.3. A positive correlation was found between SurvivinmRNA in peripheral blood and Survivin protein in tissues. It suggested that detecting SurvivinmRNA in peripheral blood could replace detecting Survivin protein in tissues.4. It was found a strong correlation between efficacy and ACECs> A Survivin mRNA^ ACYFRA21-1 orACEA in lung caner. It showed these markers could be predicted efficacy.5. There was positive correlation between A CECs -, A Survivin mRNA -> A CEA in lung adenic caner or A CECs and A CYFRA21-lor A Survivin mRNA in lung squamosal caner. It suggested the variation of these markers after treatment could be ganged.6. ACECsandTTP ntreatment method was influential factor of long-term survival time.