FOXA1 Expression And Clinical Correlation In Prostate Cancer

Prostate cancer(PCa) is the most common malignant tumor in male reproductive system. The incidence of this disease increases along with the age growth and has obvious regional and ethnic difference, which is much higher in Europe and America. PCa is the second leading cause of death of cancer in men, second only to lung cancer [1, 2]. In our country, the incidence of PCa also exhibits a trend of increase and there are statistics show that there is a big difference between the incidence in urban and rural. Present studies have found that the pathogenesis of PCa is related with many cancer genes such as NKX3.1, Ras, Myc, Sis, Fos, her1(erb B1), her2(erb B2) and also involves many signaling pathways, such as PI3K-Akt-m TOR, Ras-Raf-Mek-MAPK, Stat, etc. Forkhead- box A1(FOXA1) gene,which is also called hepatoeyte nuclear factor 3 a(HNF3a) gene, is a member of transcription factors FOX family[3] and plays an important role in the differentiation of epithelial cell. Present studies have established that FOXA1 is expressed in many human organs, such as breast, lung, esophagus, liver, pancreas, bladder, prostate and so on[4-6] and can combine to multiple gene promoters to regulate cell signaling and cell cycle [7, 8]. But the relationship between FOXA1 and PCa has not been reported in domestic researches and only several studies involve this relationship in foreign researches. To explore the correlation between FOXA1 and PCa, this study combines paraffin specimens and fresh tissue specimens and use immunohistochemical staining, Western blot, Real-Time PCR to observe the location and expression of FOXA1 in PCa and benign prostatic hyperplasia(BPH) from the level of protein and nucleic acid. Combined with clinical data, we also analyzed the relationship between FOXA1 positive expression rate and patients’ age, the tumor TNM staging and Gleason grading.The design of experiment is as follows:Objective: Explore the relationship between FOXA1 positive expression rate and patients’ age, the tumor TNM staging and Gleason grading.Methods: Collect 35 paraffin specimens of prostate cancer radical surgery and prostate biopsy and 21 paraffin specimens after electric resection of prostatic hyperplasia and use immunohistochemical staining to detect the localization and expression FOXA1 protein; Collect 21 frozen tissues after prostate cancer radical surgery and 21 frozen tissues after electric resection of prostatic hyperplasia and use Western blot and Real Time-PCR to detect the expression of FOXA1 protein and nucleic acid; Use statistical software to analysis mutual relations between FOXA1 m RNA transcription and total protein expression.Results: 1. The result of immunohistochemical staining showed that FOXA1 was both expressed in prostate cancer and prostate hyperplasia tissues and was located in prostate gland epithelial cell nuclei. The expression of FOXA1 in prostate cancer tissue is significantly higher than in the prostate hyperplasia tissue(P<0.001). 2. Through a quantitative analysis, the result of immunohistochemical staining showed that the expression of FOXA1 had no obvious correlation with the patients’ age, but was positively correlated with Gleason score(P=0.027) and tumor TNM stage(P=0.003). 3. The result of Western-blot test showed that within the cell total protein, the expression of FOXA1 protein in prostate cancer tissue was significantly higher than in the prostate hyperplasia tissue(P < 0.001).4. The result of RT-PCR detection showed that the FOXA1 transcription m RNA in prostate cancer tissue was significantly higher than in the prostate hyperplasia tissue(P<0.001).Conclusion: 1.FOXA1 m RNA and protein are both highly expressed in prostate cancer, which suggests FOXA1 is highly correlated with prostate cancer. 2. The higher the Gleason score and TNM staging of prostate cancer is, the more the expression of FOXA1 is, which prompts the positive expression of FOXA1 is associated with the malignant degree of prostate cancer. 3. The expression of FOXA1 m RNA and protein were positively correlated with each other in prostate cancer, which suggests FOXA1 is involved in regulating the process of the occurrence and development of prostate cancer.