Expression And Clinical Significance Of Autophagy Gene Beclin-1 In Prostate Cancer

Autophagy is a significant physiologic process which preformed primary lysosomes process endogenous substrates in eukaryotic cells. Life can maintain protein metabolism and cellular homeostasis by autophagy. It plays an important role in cellular waste removal, rebuilding the structure, growth and development, which is strongly associated with the occurrence of the disease. At present, there has been found three main forms of autophagy: macroautophagy, microautophagy and chaperone mediated autophagy(CMA). Macroautophagy is what is commonly called autophagy. It is currently known several autophagy regulatory pathways, including Beclin-1 signal pathway, m TOR(Mammalian Target of Rapamycin)signal pathway, Autophagy Related Gene, Atg and Ubiquitin-link system. Autophagy gene Beclin-1 is homologous with yeast autophagy gene Atg6, which is located in the chromosome 17q21, encoding a protein of 450 amino acid sequence. Beclin-1 helps the formation of mammalian autophagosome in Golgi body, which is important to the location of other autophagy proteins in anterior autophagosome.Prostate cancer is a common male malignant carcinoma. The morbidity in China has a rising trend in recent years. Deprivation of androgen therapy is often used in the treatment of advanced prostate cancer. However, most of the patients will eventually turn into castrate-resistant prostate cancer(CRPC). CRPC has poor clinical outcome using traditional withdrawal of androgen therapy. Autophagy plays an important role in CRPC. Autophagy gene Beclin-1 is expressed at low level in a variety of tumor tissues, which has indicated that autophagy principally serves an adaptive role in the progress of prostate cancer. In this paper immunohistochemistry technique was used to detect theexpression of Beclin-1 among prostate cancer cases, and to explore its correlation with relevant clinical and pathological factors.132 pathological specimens were taken from rectum prostate biopsy, and all of these specimens were pathologically proved prostate adenocarcinoma. Two groups were involved in the study. The experiment group was prostatic adenocarcinoma tissue and the control group was benign prostatic hyperplasia tissue. Each specimen included in the study was at least one needle for benign prostatic hyperplasia tissue(paracancerous tissue). All the cases were processing through immunohistochemical staining, and the specimen would be incorporated into the positive group if there were any positive expression. In contrast, when the specimen had negative expression, it would be incorporated into the negative group. Super Vision immunohistochemistry technique was used to detect the expression of Beclin-1 among 132 prostate cancer cases and paracancerous cases. The correlations between the expression of Beclin-1 and the clinical significance were analyzed.The results showed as follows: 1. Beclin-1-positive color was tan, which were expressing in the cytoplasm. The positive incidence of Beclin-1 expression in prostate cancer tissues was significantly lower than paracancerous tissues, with figure standing at 38.6% and 54.5% respectively. 2. 132 specimens were divided into three groups by Gleason Grade:grade 2~4;grade 5~7;more than grade 8. The expression rates of Beclin-1 were lower in the groups with high Gleason Grade, which were 66.7%,39.7% and 27.3% separately,and the difference among the groups was statistically significant. 3. The Beclin-1 expression was associated with lymph node metastases and bone metastases(P < 0.05).while showed no statistic significance in age, family history and prostatitis history(P < 0.05). 4. 76 cases were experienced radical prostatectomy and PSA level detection at three months follow-up. The PSA level of 10 cases were equal orgreater than 0.02ng/ml,with 2 cases having positive incidence of Beclin-1 expression. The PSA level of 66 cases was less than 0.02ng/ml. Among those, 42 cases had positive incidence of Beclin-1 expression. The positive rate showed 20% and 63.6% respectively, and the difference was statistically significant(P < 0.05). It thus appears that the expression of autophagy gene Beclin-1 decreases in prostate cancer and is related to lymph node metastases, bone metastases and biochemical recurrence. The decreasing indicates tumorigenesis and development. Therefore, Beclin-1 could be a novel diagnostic and therapeutic approach to prostate cancer at late stage.