Limits...
Upregulation of RASGRP3 expression in prostate cancer correlates with aggressive capabilities and predicts biochemical recurrence after radical prostatectomy.

Zeng X, Hu Z, Wang Z, Tao J, Lu T, Yang C, Lee B, Ye Z - Prostate Cancer Prostatic Dis. (2014)

Bottom Line: PCa with RasGRP3-positive expression may increase the risk of PSA recurrence and decrease cancer-specific survival (P=0.0291 and P=0.0044).The expression of RasGRP3 was also associated with PSA recurrence and cancer-specific survival in univariate (P<0.001 and P<0.001) and multivariate analyses (P<0.001 and P=0.003).RasGRP3 mRNA and proteins were found to be positively expressed in PCa cell lines.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Tonji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

ABSTRACT

Background: This study was undertaken to investigate the expression of guanyl nucleotide-releasing protein for Ras 3 (RasGRP3) in the cell lines and tissues in BPH and prostate cancer (PCa), as well as its associations with cancer invasion and prognosis in prostate carcinomas.

Methods: Expression analysis of RasGRP3 was accomplished using immunohistochemical staining of PCa and BPH tissues. Pearson's χ2 test was used to analyze the association between RasGRP3 expression and specific clinical parameters. Survival and PSA relapse curves were evaluated using the Kaplan-Meier curves and log-rank tests, and the differences were assessed using the Cox regression methods. In addition, human PCa cell lines PC-3, DU145, LNCaP, PC3M-1E8, PC3M-2B4 and BPH-1 were examined for expression of RasGRP3 using western blot and quantitative polymerase chain reaction (Q-PCR) analysis. After PC-3 cells were transfected by small interfering RNA targeting RasGRP3, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and migratory assays were employed to determine the vitality and aggressive capability of tumor cell in vitro.

Results: Expression of RasGRP3 was significantly correlated (P=0.038 and P=0.021) with Gleason score (< or =6 versus > or =7) and T stage (T1-T2 versus T3-T4), respectively. PCa with RasGRP3-positive expression may increase the risk of PSA recurrence and decrease cancer-specific survival (P=0.0291 and P=0.0044). The expression of RasGRP3 was also associated with PSA recurrence and cancer-specific survival in univariate (P<0.001 and P<0.001) and multivariate analyses (P<0.001 and P=0.003). RasGRP3 mRNA and proteins were found to be positively expressed in PCa cell lines. There was higher expression of RasGRP3 in PC-3, DU145 and PC3M-1E8 than in LNCaP, PC3M-2B4 and BPH-1. Knockdown of RasGRP3 inhibited the proliferation, migration and invasion capabilities of PC-3 cells.

Conclusions: These data suggested that elevated RasGRP3 expression may play a key role in the malignant progression of PCa, especially in invasion and metastasis, and may be a potential marker of biochemical recurrence.

Show MeSH

Related in: MedlinePlus

Correlation of prostate cancer (PCa) risk and guanyl nucleotide-releasing protein for Ras 3 (RasGRP3) protein expression. PCa risk groups were stratified by low-risk groups (n=15), intermediate-risk groups (n=20) and high-risk groups (n=18), according to the National Comprehensive Cancer Network Guidelines. Immunostaining score of RasGRP3 protein expression was determined by immunohistochemistry.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4020276&req=5

fig2: Correlation of prostate cancer (PCa) risk and guanyl nucleotide-releasing protein for Ras 3 (RasGRP3) protein expression. PCa risk groups were stratified by low-risk groups (n=15), intermediate-risk groups (n=20) and high-risk groups (n=18), according to the National Comprehensive Cancer Network Guidelines. Immunostaining score of RasGRP3 protein expression was determined by immunohistochemistry.

Mentions: In order to have a better understanding of its potential predictive value in PCa progression, the relationship between RasGRP3 (ISS) and PCa risk was analyzed. PCa patients were stratified to low-, intermediate- and high-risk groups, according to National Comprehensive Cancer Network (NCCN) Guidelines.16 As shown in Figure 2, ISSs revealed significant difference in RasGRP3 levels among three PCa risk groups (P<0.001). More importantly, increased RasGRP3 protein expression was correlated with enhanced PCa risk. For instance, the average ISSs of low-, intermediate- and high-risk groups were 5.47±1.64, 8.30±1.34 and 10.44±1.62, respectively. Taken together, these observations illustrated that RasGRP3 is frequently upregulated in PCa with worse clinical and pathological parameters and has potential predictive value for evaluating increased PCa risk.


Upregulation of RASGRP3 expression in prostate cancer correlates with aggressive capabilities and predicts biochemical recurrence after radical prostatectomy.

Zeng X, Hu Z, Wang Z, Tao J, Lu T, Yang C, Lee B, Ye Z - Prostate Cancer Prostatic Dis. (2014)

Correlation of prostate cancer (PCa) risk and guanyl nucleotide-releasing protein for Ras 3 (RasGRP3) protein expression. PCa risk groups were stratified by low-risk groups (n=15), intermediate-risk groups (n=20) and high-risk groups (n=18), according to the National Comprehensive Cancer Network Guidelines. Immunostaining score of RasGRP3 protein expression was determined by immunohistochemistry.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4020276&req=5

fig2: Correlation of prostate cancer (PCa) risk and guanyl nucleotide-releasing protein for Ras 3 (RasGRP3) protein expression. PCa risk groups were stratified by low-risk groups (n=15), intermediate-risk groups (n=20) and high-risk groups (n=18), according to the National Comprehensive Cancer Network Guidelines. Immunostaining score of RasGRP3 protein expression was determined by immunohistochemistry.
Mentions: In order to have a better understanding of its potential predictive value in PCa progression, the relationship between RasGRP3 (ISS) and PCa risk was analyzed. PCa patients were stratified to low-, intermediate- and high-risk groups, according to National Comprehensive Cancer Network (NCCN) Guidelines.16 As shown in Figure 2, ISSs revealed significant difference in RasGRP3 levels among three PCa risk groups (P<0.001). More importantly, increased RasGRP3 protein expression was correlated with enhanced PCa risk. For instance, the average ISSs of low-, intermediate- and high-risk groups were 5.47±1.64, 8.30±1.34 and 10.44±1.62, respectively. Taken together, these observations illustrated that RasGRP3 is frequently upregulated in PCa with worse clinical and pathological parameters and has potential predictive value for evaluating increased PCa risk.

Bottom Line: PCa with RasGRP3-positive expression may increase the risk of PSA recurrence and decrease cancer-specific survival (P=0.0291 and P=0.0044).The expression of RasGRP3 was also associated with PSA recurrence and cancer-specific survival in univariate (P<0.001 and P<0.001) and multivariate analyses (P<0.001 and P=0.003).RasGRP3 mRNA and proteins were found to be positively expressed in PCa cell lines.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Tonji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

ABSTRACT

Background: This study was undertaken to investigate the expression of guanyl nucleotide-releasing protein for Ras 3 (RasGRP3) in the cell lines and tissues in BPH and prostate cancer (PCa), as well as its associations with cancer invasion and prognosis in prostate carcinomas.

Methods: Expression analysis of RasGRP3 was accomplished using immunohistochemical staining of PCa and BPH tissues. Pearson's χ2 test was used to analyze the association between RasGRP3 expression and specific clinical parameters. Survival and PSA relapse curves were evaluated using the Kaplan-Meier curves and log-rank tests, and the differences were assessed using the Cox regression methods. In addition, human PCa cell lines PC-3, DU145, LNCaP, PC3M-1E8, PC3M-2B4 and BPH-1 were examined for expression of RasGRP3 using western blot and quantitative polymerase chain reaction (Q-PCR) analysis. After PC-3 cells were transfected by small interfering RNA targeting RasGRP3, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and migratory assays were employed to determine the vitality and aggressive capability of tumor cell in vitro.

Results: Expression of RasGRP3 was significantly correlated (P=0.038 and P=0.021) with Gleason score (< or =6 versus > or =7) and T stage (T1-T2 versus T3-T4), respectively. PCa with RasGRP3-positive expression may increase the risk of PSA recurrence and decrease cancer-specific survival (P=0.0291 and P=0.0044). The expression of RasGRP3 was also associated with PSA recurrence and cancer-specific survival in univariate (P<0.001 and P<0.001) and multivariate analyses (P<0.001 and P=0.003). RasGRP3 mRNA and proteins were found to be positively expressed in PCa cell lines. There was higher expression of RasGRP3 in PC-3, DU145 and PC3M-1E8 than in LNCaP, PC3M-2B4 and BPH-1. Knockdown of RasGRP3 inhibited the proliferation, migration and invasion capabilities of PC-3 cells.

Conclusions: These data suggested that elevated RasGRP3 expression may play a key role in the malignant progression of PCa, especially in invasion and metastasis, and may be a potential marker of biochemical recurrence.

Show MeSH
Related in: MedlinePlus