The Correlations Between The Expression Of Annexin â…¡ And Clinicopathologic Features And Progression Of Prostate Cancer

Objective:The aim of our work is to investigate the correlations between the expression of annexin Ⅱ and Clinicopathologic features as well as prognosis of prostate cancer (PC), and then explore the role of annexin Ⅱ in the development of prostate cancer.Methods:All prostate specimens were paraffin-embedded in paraffins and confirmed by the pathological diagnosis. They were divided into two groups:40BPH,85PC. The85PC were further divided into various groups according to Gleason’s criterion, Prostate-specific antigen(PSA), risk PC, clinical stage. Expression of annexin Ⅱ was determined by immunohistochemical staining. The correlation among Expression of annexin Ⅱ and clinicopathologic features were evaluated through retrospective study. The relationship between the expression of annexin Ⅱ and the survival time of PC were analyzed by SPSS software. The independent prognosis factors were analyzed by Cox’s proportional hazards model.Results:(1) The results from immunohistochemical staining showed that the positive ratio of annexin Ⅱ expression were62.4%(53/85) in PC, and92.5%(37/40) in BPH. And there were significant difference between the expression of annexin Ⅱ and PC as well as BPH (P<0.05).(2) The positive ratio of annexin Ⅱ expression were77.5%(31/40)、58.3%(21/36).11.1%(1/9)in the case of Gleason2-4,5-7and8-10in PC, respectively. And there were significant difference of the expression of annexin Ⅱ among them (P<0.05).(3) The positive ratio of annexin Ⅱ expression were78.3%(36/46)、57.1%(16/28).9.1%(1/11) in the case of PSA (prostate specific antigen)<10ng/ml,10-20ng/ml, and>20ng/ml in PC, respectively. And there were significant difference of the expression of annexin Ⅱ among them (P<0.05). There were negative interrelation between the expression of annexin Ⅱ and PSA quantities.(4) The positive ratio of annexin Ⅱ expression were80.9%(38/47)、54.2%(13/24)、14.3%(2/14)in low risk, moderate risk and high risk of PC, respectively. And there were significant difference of the expression of annexin Ⅱ among them (P<0.05).(5) By retrospective study, there were positive interrelation between the expression of annexin Ⅱ and clinical stages, recurence, lymph node metastasis and distant metastasis (P<0.05).(6) Kaplan-Meier survival curve showed that PC patients with low or negative expression of annexin Ⅱ seem to have a poorly survival rate in comparison to those with positive and strong expression of annexin Ⅱ.(7) Prognosis analysis showed that PC patients with low or negative expression of annexin Ⅱ, clinical stages over T3, Gleason>7, PSA>20ng/mL, and with lymph node metastasis and distant metastasis, seem to have poorly prognosis, and annexin Ⅱ can serve as independent index of prognosis in PC.Conclusion:(1) Our study indicated that there was close correlations with the expression of annexin Ⅱ and PC. It appeared to that the annexin Ⅱ could be used as the basis index of early diagnosis for PC.(2) There were close correlations between the expression of annexin II in PC and Gleason scores, PSA level, risk of PC, clinical stage. It seemed that annexin Ⅱ play a key role in the development of prostate cancer.(3) There were close interrelation betweent the downregulation of annexin Ⅱ and decreasing survival rate in PC, and to detect the expression of annexin Ⅱ could serve as an independent factor to the survival analysis and prognosis decision in PC. Objective:To study the correlations betweent the downregulation of annexin Ⅱ and progression of PC, and investigate the mechanism of decreasing annexin Ⅱ in PC metastasis.Methods:The expression of annexin Ⅱ in three kinds of cell lines with different metastasis potency as follows:LNCaP(low metastasis potency), PC-3(low metastasis potency), C4-2B (high metastasis potency), were detected by western blot. The correlations between the expression of annexin Ⅱ and the metastasis ability of PC were analyzed. After RNAi was performed in PC-3cells to downregulate the expression of anndxin Ⅱ, at first, cell proliferation assay was performed by MTT method, then cell apoptosis level was detected by flow cytometry, and then the expression of MMP-2and MMP-9were detected by western blot, and then in vitro cell’s invasive ability was detected by transwell cabinet test, at last migration ability of PC-3cells was detected by scratch test.Results:(1) The expression of annexin Ⅱ were lower in C4-2B cells with high metastasis potency than those of LNCaP and PC-3cells with low metastasis potency. And there were significant difference of the expression of annexin Ⅱ between them (P<0.05).(2) After RNAi was performed in PC-3cells to downregulate the expression of annexin Ⅱ, the growth speed was faster in PC-3-ANXA2-siRNA cells than in PC-3、PC-3-Lip、PC-3-empty vector (P<0.05)cells. The downregulation of annexin Ⅱ could promote the growth of PC cells.(3) After RNAi was performed in PC-3cells to downregulate the expression of annexin Ⅱ, the percent ratio of apoptosis detected by flow cytometry in PC-3、PC-3-Lip、PC-3-empty vector and PC-3-ANXA2-siRNA cells were2.3±1.98、2.1±2.01、2.0±1.81、6.2±2.59, respectively. And the apoptosis ratio in PC-3-ANXA2-siRNA cells was the highest(P>0.05), but there were no significant difference compare to others.(4) After RNAi were performed in PC-3cells to downregulate the expression of annexin Ⅱ, the expression of annexin Ⅱ in PC-3-ANXA2-siRNA cells were decreased while the expression of MMP-2and MMP-9were increased.(5) After RNAi was performed in PC-3cells to downregulate the expression of annexin Ⅱ, in vitro invasive ability of PC-3-ANXA2-siRNA cells detected by transwell cabinet test was increased.(6) After RNAi were performed in PC-3cells to downregulate the expression of annexin Ⅱ, in vitro migrate ability of PC-3-ANXA2-siRNA cells detected by scratch test was increased.Conclusion:(1) Downregulation of annexin Ⅱ could promote the growth of PC cell, and annexin Ⅱ could serve as a growth inhibitor of PC cell.(2) There were close interrelation betweent the expression of annexin Ⅱ and metastasis ability of PC, and annexin Ⅱ could serve as a metastasizing biomarker.(3) The downregulation of annexin Ⅱ could increase the ability of metastasis and migration in vitro, and may be come true through the upregulation of MMP-2and MMP-9expression.