Limits...
Protease Activated Receptors 1 and 2 Correlate Differently with Breast Cancer Aggressiveness Depending on Tumor ER Status.

Lidfeldt J, Bendahl PO, Forsare C, Malmström P, Fernö M, Belting M - PLoS ONE (2015)

Bottom Line: We find that PAR-2 associates with DDFS (HR = 3.1, P = 0.003), whereas no such association was found with PAR-1 (HR = 1.2, P = 0.6).HR = 1.2 in ER-negative; P = 0.045 for differential effect), and PAR-2 was an independent prognostic factor specifically in ER-positive tumors (HR = 3.9, P = 0.045).HR = 0.5, P = 0.19 in ER-positive; P = 0.026 for differential effect).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences, Section of Oncology and Pathology, Lund University, Lund, Sweden.

ABSTRACT
Experimental models implicate protease activated receptors (PARs) as important sensors of the proteolytic tumor microenvironment during breast cancer development. However, the role of the major PARs, PAR-1 and PAR-2, in human breast tumors remains to be elucidated. Here, we have investigated how PAR-1 and PAR-2 protein expression correlate with established clinicopathological variables and patient outcome in a well-characterized cohort of 221 breast cancer patients. Univariable and multivariable hazard ratios (HR) were estimated by the Cox proportional hazards model, distant disease-free survival (DDFS) and overall survival by the Kaplan-Meier method, and survival in different strata was determined by the log-rank test. Associations between PARs and clinicopathological variables were analyzed using Pearson's χ2-test. We find that PAR-2 associates with DDFS (HR = 3.1, P = 0.003), whereas no such association was found with PAR-1 (HR = 1.2, P = 0.6). Interestingly, the effect of PAR-2 was confined to the ER-positive sub-group (HR = 5.5, P = 0.003 vs. HR = 1.2 in ER-negative; P = 0.045 for differential effect), and PAR-2 was an independent prognostic factor specifically in ER-positive tumors (HR = 3.9, P = 0.045). On the contrary, PAR-1 correlated with worse prognosis specifically in the ER-negative group (HR = 2.6, P = 0.069 vs. HR = 0.5, P = 0.19 in ER-positive; P = 0.026 for differential effect). This study provides novel insight into the respective roles of PAR-1 and PAR-2 in human breast cancer and suggests a hitherto unknown association between PARs and ER signaling that warrants further investigation.

No MeSH data available.


Related in: MedlinePlus

One minus distant disease-free survival (DDFS) stratified by PARs.Prognosis in relation to PAR-2 (a) and PAR-1 (b) status in the entire cohort.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526525&req=5

pone.0134932.g001: One minus distant disease-free survival (DDFS) stratified by PARs.Prognosis in relation to PAR-2 (a) and PAR-1 (b) status in the entire cohort.

Mentions: In univariable analysis, PAR-2 was a prognostic factor for DDFS (HR: 3.1, 95% CI: 1.5–6.4, P = 0.003), whereas PAR-1 showed no such correlation (HR: 1.2, 95% CI: 0.6–2.3, P = 0.6) (Table 3). The DDFS was 92 and 76% in low- and high-PAR-2 expressing groups, respectively (Fig 1A). In univariable analysis of BCM during the first 10 years after diagnosis, PAR-2 remained as a significant prognostic factor (HR: 2.4, 95% CI: 1.3–4.5, P = 0.006) (Table 3). The corresponding cumulative BCM (95% CI) was 13% (7–19%) and 27% (19–36%) in low- and high-PAR-2 expressing groups, respectively (S2A Fig). Overall, HER-2, PAR-2, Ki-67, histological grade, ER age and PR were significant prognostic factors in univariable analysis of DDFS whereas tumor size and PAR-1 were not significantly associated to DDFS (Table 3and Fig 1B).


Protease Activated Receptors 1 and 2 Correlate Differently with Breast Cancer Aggressiveness Depending on Tumor ER Status.

Lidfeldt J, Bendahl PO, Forsare C, Malmström P, Fernö M, Belting M - PLoS ONE (2015)

One minus distant disease-free survival (DDFS) stratified by PARs.Prognosis in relation to PAR-2 (a) and PAR-1 (b) status in the entire cohort.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526525&req=5

pone.0134932.g001: One minus distant disease-free survival (DDFS) stratified by PARs.Prognosis in relation to PAR-2 (a) and PAR-1 (b) status in the entire cohort.
Mentions: In univariable analysis, PAR-2 was a prognostic factor for DDFS (HR: 3.1, 95% CI: 1.5–6.4, P = 0.003), whereas PAR-1 showed no such correlation (HR: 1.2, 95% CI: 0.6–2.3, P = 0.6) (Table 3). The DDFS was 92 and 76% in low- and high-PAR-2 expressing groups, respectively (Fig 1A). In univariable analysis of BCM during the first 10 years after diagnosis, PAR-2 remained as a significant prognostic factor (HR: 2.4, 95% CI: 1.3–4.5, P = 0.006) (Table 3). The corresponding cumulative BCM (95% CI) was 13% (7–19%) and 27% (19–36%) in low- and high-PAR-2 expressing groups, respectively (S2A Fig). Overall, HER-2, PAR-2, Ki-67, histological grade, ER age and PR were significant prognostic factors in univariable analysis of DDFS whereas tumor size and PAR-1 were not significantly associated to DDFS (Table 3and Fig 1B).

Bottom Line: We find that PAR-2 associates with DDFS (HR = 3.1, P = 0.003), whereas no such association was found with PAR-1 (HR = 1.2, P = 0.6).HR = 1.2 in ER-negative; P = 0.045 for differential effect), and PAR-2 was an independent prognostic factor specifically in ER-positive tumors (HR = 3.9, P = 0.045).HR = 0.5, P = 0.19 in ER-positive; P = 0.026 for differential effect).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences, Section of Oncology and Pathology, Lund University, Lund, Sweden.

ABSTRACT
Experimental models implicate protease activated receptors (PARs) as important sensors of the proteolytic tumor microenvironment during breast cancer development. However, the role of the major PARs, PAR-1 and PAR-2, in human breast tumors remains to be elucidated. Here, we have investigated how PAR-1 and PAR-2 protein expression correlate with established clinicopathological variables and patient outcome in a well-characterized cohort of 221 breast cancer patients. Univariable and multivariable hazard ratios (HR) were estimated by the Cox proportional hazards model, distant disease-free survival (DDFS) and overall survival by the Kaplan-Meier method, and survival in different strata was determined by the log-rank test. Associations between PARs and clinicopathological variables were analyzed using Pearson's χ2-test. We find that PAR-2 associates with DDFS (HR = 3.1, P = 0.003), whereas no such association was found with PAR-1 (HR = 1.2, P = 0.6). Interestingly, the effect of PAR-2 was confined to the ER-positive sub-group (HR = 5.5, P = 0.003 vs. HR = 1.2 in ER-negative; P = 0.045 for differential effect), and PAR-2 was an independent prognostic factor specifically in ER-positive tumors (HR = 3.9, P = 0.045). On the contrary, PAR-1 correlated with worse prognosis specifically in the ER-negative group (HR = 2.6, P = 0.069 vs. HR = 0.5, P = 0.19 in ER-positive; P = 0.026 for differential effect). This study provides novel insight into the respective roles of PAR-1 and PAR-2 in human breast cancer and suggests a hitherto unknown association between PARs and ER signaling that warrants further investigation.

No MeSH data available.


Related in: MedlinePlus