Expression And Significance Of EN-2 And VEGF In Prostate Cancer

Background:Prostate cancer（PCa）is a common malignant tumor disease in urological elderly men.In the world,the incidence of prostate cancer ranks second among all malignant tumors in men^[1],and its mortality rate ranks first.Sixth,the incidence of prostate cancer in the United States has surpassed lung cancer,becoming the first malignant tumor that harms men’s health^[2,3].There are significant geographical and ethnic differences in the incidence of prostate cancer,with the highest incidence rates in Australia,New Zealand,the Caribbean,and Scandinavia,and lower in Asia and North Africa^[1,4-9].In recent years,the incidence of prostate cancer in Asian countries has shown a clear upward trend,and the growth rate is faster than that of developed countries in Europe and America.In China,the incidence of prostate cancer in men under 60 years old is low,and the incidence rate is higher than 60 years old^[10].The increase of prostate cancer incidence in China may be related to the gradual increase of aging in China’s society,diet structure and living habits.Constant changes,continuous improvement in the level of diagnosis and treatment and other factors^[11].Early prostate cancer has a good prognosis.Because early treatments have an effect on them,because early prostate cancer surgery can achieve the effect of radical cure.PCa patients diagnosed with T1,T2 or T3 had a higher 5-year survival rate,and the5-year survival rate of advanced prostate cancer decreased significantly.The 5-year survival rate of patients with T4 was less than 27%^[12].It is noteworthy that 5%of the global deaths from prostate cancer are in China^[10,13],mainly due to the fact that nearly 2/3 of the patients in the country have had local or distant metastasis at the time of initial diagnosis and lost their radical cure.Opportunistic surgery opportunities,while in the United States,81%of cases of localized prostate cancer,lymph node and distant metastasis accounted for only 12%and 4%^[10,14,15].From this point of view,early diagnosis of prostate cancer is very important.Prostate cancer lacks specific symptoms early,and most patients have metastasized when they see the following urinary tract obstruction.Prostate cancer can progress to an incurable stage without symptoms,and the only way to avoid this outcome is through active screening^[16,17].At present,the most commonly used prostate cancer screening method in clinical work is the detection of prostate specific antigen（PSA）in the blood.Although the extensive clinical promotion of PSA detection has greatly improved the early diagnosis rate of prostate cancer,but PSA specific The lower sex,resulting in a higher rate of negative prostate biopsy results,also increased the number of repeated punctures.Especially in people with PSA levels between 4 and 10 ng/mL,the negative rate of prostate biopsy is close to 60%to 75%^[18],which increases unnecessary diagnostic operations and results in harm to patients.Sexuality exceeds the expected benefits.The inadequacy of PSA testing has prompted attempts to find markers of prostate cancer that can compensate for these defects^[19].A new,high-sensitivity,high-specificity prostate cancer screening index is urgently needed in the clinic,which can greatly improve the early detection rate of prostate cancer,reduce the frequency of PSA detection and reduce additional testing items..The Engrailed-2 protein is a class of homeobox proteins encoded by the Engrailed-2（EN-2）gene,which contains a 60 amino acid structural and functionally highly conserved homology domain.As early as 1929,Professor Eker discovered the Engrailed gene for the first time in the spontaneous mutation of Drosophila melanogaster.Professor Peel et al.in 2006 proposed a systematic evolution analysis of the EN gene:The EN gene exists as a conserved gene cassette.The entire evolution of insects.The human Engrailed-2 gene is located on chromosome 7q36.In recent years,it has been found to be abnormally expressed in human breast cancer cells^[20],renal clear cell carcinoma tissues^[21],and bladder cancer tissues^[22].EN2 is likely to be a potential tumor marker for a variety of tumors.Vascular endothelial growth factor（VEGF）is one of the most important factors in promoting angiogenesis.Many studies have confirmed that VEGF can specifically act on vascular endothelial cells,effectively promote the growth of vascular endothelial cells,accelerate the rate of angiogenesis,and enable new life.Increased permeability of blood vessels is closely related to tumor cell infiltration and metastasis in tumor tissues^[23].This topic combines Engrailed-2 protein with vascular endothelial growth factor（VEGF）to study two important proteins,explore the characteristics and correlation of Engrailed-2 and VEGF expression in prostate cancer,and enrich the prostate.The theoretical knowledge of cancer tumor marker detection can provide new ideas for early diagnosis and treatment of prostate cancer diseases.Objective:1.The significance of Engrailed-2 and VEGF expression in prostate cancer tissues.2.The relationship between Engrailed-2 and VEGF and some clinical parameters of prostate cancer patients.3.Correlation between Engrailed-2 and VEGF expression in prostate cancer.Method:The prostate cancer tissues of the First Affiliated Hospital of Zhengzhou University were collected after radical prostatectomy or prostate puncture.Another 45cases of benign prostatic hyperplasia were randomly collected.The EN-2 protein was analyzed by immunohistochemistry.The difference of VEGF protein expression between prostate cancer and benign prostatic hyperplasia tissues,and the relationship between EN-2 protein and VEGF protein and some clinical parameters of prostate cancer patients.The results were statistically analyzed usingχ2 test and Spearman rank correlation analysis.The significance test level was p<0.05.Results:1.Immunohistochemistry showed that the expression of EN2 protein in prostate cancer tissues was significantly higher than that in benign prostatic hyperplasia tissues,mainly in the cytoplasm of prostate gland epithelial cells.The positive rates of EN2 protein expression in prostate cancer tissues and benign prostatic hyperplasia tissues were 88.33%（53/60）and 11.11%（5/45）,respectively.The difference was statistically significant（P<0.05）.The positive rates of EN2 in the Gleason≥8 and Gleason<8 groups were 97.30%（36/37）and 73.91%（17/23）,respectively.The difference was statistically significant（P<0.05）.The positive rates in the I+II group and the III+IV group were 76.92%（20/26）and 97.06%（33/34）,respectively,and the difference was statistically significant（P<0.05）.The positive rates in the lymph node positive group and the node negative group were 100%（25/25）and 76.19%（16/21）,respectively,and the difference was statistically significant（P<0.05）.The positive rates of prostate cancer in the bone metastasis group and the boneless metastasis group were 100%（13/13）and 85.11%（40/47）,respectively,and the difference was not statistically significant（P>0.05）.The positive rates of prostate cancer in the group older than 70 years and those less than 70 years old were 87.5%（14/16）and 88.63%（39/44）,respectively（P>0.05）,and the difference was not statistically significant.The positive rates in the smoking group and the non-smoking group were 90.63%（29/32）and 85.71%（24/28）,respectively,and the difference was not statistically significant（P>0.05）.The positive rates of the seminal vesicle involvement group and the non-sperm cystic gland involvement group were 90.4%（19/21）and 86.67%（26/30）,respectively,and the difference was not statistically significant（P>0.05）.The positive rates in the margin-positive group and the margin-negative group were 96.77%（30/31）and 77.27%（17/22）,respectively,and the difference was not statistically significant（P>0.05）.2.Immunohistochemistry showed that the expression of VEGF protein in prostate cancer tissues was significantly higher than that in benign prostatic hyperplasia tissues,mainly in the cytoplasm of prostate gland epithelial cells.The positive rates of VEGF protein expression in prostate cancer tissues and benign prostatic hyperplasia tissues were 68.33%（41/60）and 26.67%（12/45）,respectively.The difference was statistically significant（P<0.05）.The positive rates of VEGF in the Gleason≥8 and Gleason<8 groups were 78.38%（29/37）and 52.17%（12/23）,respectively.The difference was statistically significant（P<0.05）.The positive rates in the I+II and III+IV groups were 46.15%（13/26）and 82.35%（28/34）,respectively,and the difference was statistically significant（P<0.05）.The positive rates in the lymph node positive group and the node negative group were 96%（24/25）and66.67%（14/21）,respectively,and the difference was statistically significant（P<0.05）.The positive rates of prostate cancer in the bone metastasis group and the boneless metastasis group were 76.92%（10/13）and 65.96%（31/47）,respectively,and the difference was not statistically significant（P>0.05）.The positive rates of prostate cancer in the group older than 70 years and those less than 70 years old were68.75%（11/16）and 68.18%（30/44）,respectively（P>0.05）,and the difference was not statistically significant.The positive rates in the smoking and non-smoking groups were 68.75%（22/32）and 67.86%（19/28）,respectively,and the difference was not statistically significant（P>0.05）.The positive rates in the seminal vesicle-affected group and the non-sperm cystic group were 76.19%（16/21）and 73.33%（22/30）,respectively,and the difference was not statistically significant（P>0.05）.The positive rates in the margin-positive group and the margin-negative group were 80.65%（25/31）and 63.64%（14/22）,respectively,and the difference was not statistically significant（P>0.05）.3.In 60 specimens of prostate cancer,EN-2 and VEGF protein were positively expressed in 36 cases,EN-2 and VEGF protein were negatively expressed in 2 cases;EN-2 and VEGF protein were expressed in prostate cancer.Positive correlation,rs=0.784（P=0.004<0.05）.Conclusion:1.Both EN2 protein and VEGF protein in prostate cancer tissues are highly expressed in benign prostatic hyperplasia tissues,and EN2 protein and VEGF protein are involved in prostate cancer.2.EN2 and VEGF were associated with Gleason score,clinical stage,and lymph node metastasis of prostate cancer,and had no significant relationship with age,smoking,and positive margin.EN2 and VEGF can be an independent risk factor for prostate cancer staging and prognosis.3.There was a positive correlation between EN2 and VEGF expression in prostate cancer,r_s=0.784（P=0.004<0.05）.