Expression And Significance Of GDF15in Prostate Cancer And Its Correlation With The Expression Of EGFR And P-Braf

ObjectiveTo examine the different expression pattern of GDF15in precancerous lesions and prostate cancers and investigate the mechanisms for abnormal expression of GDF15as well as its clinicalpathologic significance.MethodsThe expression of GDF15mRNA was detested by RT-PCR in cancerous and matched noncancerous prostate tissues from17cases of prostate carcinomas. The expression of GDF15protein was evaluated in73cases of human prostate carcinomas (43cases with gleason score≤7,30cases with gleason score>7),22cases of human high grade prostatic intraepithelial neoplasia (PIN) and23cases of human benign prostatic hyperplasis (BPH) by using immunohistochemistry (SP method) and tissue microarray. The correlations between expression of GDF15and clinicalpathologic features were analyzed. Moreover, we also tested the expression of EGFR and p-Braf in prostate cancers, and discuss the relationship between GDF15and EGFR, p-Braf. Results1. RT-PCR results for GDF15GDF15mRNA expression could be observed in17cases of prostate cancers,76.5%of which were much higher when compared with the normal tissue. Semiquantitative RT-PCR revealed that the average gray value of GDF15mRNA was0.900±0.082in prostate cancers, which was significantly higher than that in the normal tissues (0.409±0.102, P<0.05)2. IHC results for GDF15The positive rate of GDF15protein expression was83.6%(61/73),72.7%(16/22) and8.7%(2/23) in prostate carcinomas, high grade PIN and BPH respectively. Differences of the expression between prostate cancer, high grade PIN and BPH were significant (P<0.05). The positive rate of GDF15protein expression was74.4%(32/43),96.7%(29/30) in well to median-differentiated and low-differentiated prostate cancer groups. There was also a significant difference between the two groups (P<0.05). The positive rate of GDF15protein expression was87%(40/46)、77.8%(21/27) in T1-T2stage and T3-T4stage groups, which lacked a statistical difference. Additionally, there was no correlation between the expression of GDF15and the patients’age.3. IHC results for EGFR and p-BrafThe positive rates of EGFR and p-Braf protein expression in prostate cancers were72.6%(53/73) and61.6%(45/73), while they were13%(3/23) and4.3%(1/23) in BPH respectively. Differences between the two groups were significant.4. The correlation between GDF15and EGFR、p-BrafThere was a positive association between the expression of GDF15and EGFR (r=0.639, P<0.001),as well as GDF15and p-Braf (r=0.258, P<0.05), EGFR and p-Braf (r=0.273, P<0.05).Conclusion1、The expression of GDF15mRNA and protein is high in prostate cancers, which implies that it may play an important role in the occurrence and development process of prostate cancers.2、The high level of GDF15expression in high grade PIN but not in normal prostate tissue suggests that overexpression of GDF15may be an early event in the development process of prostate cancers, so that it is useful for the early diagnosis of prostate cancers to detect the different expression pattern of GDF15in normal prostate, high-grade PIN and prostate cancer tissues.3、The positive association between GDF15、EGFR、p-Braf infers that GDF15may react by EGFR/RAS/RAF/MAPK signal pathway.