Screening and identification of significant genes related to tumor metastasis and PSMA in prostate cancer using microarray analysis

摘要

Tumor metastasis is one of the causes for the high mortality rate of prostate cancer (PCa) patients, yet the molecular mechanisms of PCa metastasis are not fully understood. In our previous studies, we found that PSMA suppresses the metastasis of PCa, yet the underlying mechanism remains unknown. To identify the genes related to tumor metastasis possibly regulated by PSMA, we performed tumor metastasis PCR array assay to analyze the differentially expressed tumor metastasis-related genes. Eighty-four tumor metastasis related genes were screened in si-PSMA LNCap cells (PSMA silenced by siRNA)/LNCap cells and in PC-3/LNCap cells, respectively. Expression levels of possible related genes were verified by real-time PCR in 4 prostate cancer cell lines (LNCap, 22RV1, PC-3 and DU145) and in 85 clinical samples (12 normal, 26 benign prostatic hypertrophy and 47 prostate cancer tissues). The results showed that 10 genes (including CDH6 and CXCL12) were upregulated and 4 genes (CCL7, ITGB3, MDM2 and MMP2) were downregulated in the si-PSMA LNCap cells. There were 41 genes significantly upregulated and 15 genes downregulated in PC-3 cells when compared with LNCap cells. Eight common genes were found in both the si-PSMA and PSMA(-) groups. CDH6, MMP3, MTSS1 were further identified as PSMA-related genes in the prostate cancer cell lines and clinical samples, and their expression showed a negative correlation with the stage of prostate cancer (P<0.0001) and PSMA level (P<0.05) in clinical samples, indicating their possible involvement in PSMA-related PCa metastasis regulation. These findings may provide insights into the mechanism involved in the suppression of PCa metastasis by PSMA and its possible interacting proteins, and may provide clues for further exploration of the molecular mechanism of PCa metastasis.