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Prognostic value of RKIP and p-ERK in gastric cancer.

Fujimori Y, Inokuchi M, Takagi Y, Kato K, Kojima K, Sugihara K - J. Exp. Clin. Cancer Res. (2012)

Bottom Line: Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively.RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79).Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

ABSTRACT

Background: The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor protein (RKIP), and investigated correlations of these expressions with clinicopathological features and outcomes in gastric cancer.

Methods: Tumour samples were obtained from 105 patients with gastric adenocarcinomas who underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK), phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical staining.

Results: Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively correlated with the depth of invasion (p < 0.001), lymph node involvement (p = 0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression had slightly, but not significantly shorter RFS than those without such expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001). The combination of RKIP and p-ERK expression was an independent prognostic factor (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008).

Conclusions: Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival. Negative RKIP expression combined with positive p-ERK expression was an independent predictor of poor outcomes in patients with gastric cancer.

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Kaplan-Meier curves for the relapse-free survival of patients with expression of RKIP and p-ERK.
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Figure 2: Kaplan-Meier curves for the relapse-free survival of patients with expression of RKIP and p-ERK.

Mentions: RKIP expression was associated with significantly longer RFS (p = 0.003), whereas p-MEK was not (p = 0.79). The presence of p-ERK expression was associated with slightly, but not significantly shorter RFS than the absence of such expression (p = 0.054) (Table 3). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001) (Figure 2). The prognostic relevance of positive p-ERK expression combined with negative RKIP expression was therefore assessed using a multivariate proportional-hazards model adjusted for established clinical prognostic factors (i.e., age, gender, histopathology, depth of invasion, lymph node involvement). The combination of RKIP and p-ERK expression was found to be an independent prognostic factor (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3 - 4.6; p = 0.008). Histopathological type and depth of invasion were also independent prognostic factors (HR, 2.1; 95% CI, 1.0 - 4.2; p = 0.043 and HR, 4.7; 95% CI, 1.0-22; p = 0.048, respectively) (Table 3).


Prognostic value of RKIP and p-ERK in gastric cancer.

Fujimori Y, Inokuchi M, Takagi Y, Kato K, Kojima K, Sugihara K - J. Exp. Clin. Cancer Res. (2012)

Kaplan-Meier curves for the relapse-free survival of patients with expression of RKIP and p-ERK.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351370&req=5

Figure 2: Kaplan-Meier curves for the relapse-free survival of patients with expression of RKIP and p-ERK.
Mentions: RKIP expression was associated with significantly longer RFS (p = 0.003), whereas p-MEK was not (p = 0.79). The presence of p-ERK expression was associated with slightly, but not significantly shorter RFS than the absence of such expression (p = 0.054) (Table 3). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001) (Figure 2). The prognostic relevance of positive p-ERK expression combined with negative RKIP expression was therefore assessed using a multivariate proportional-hazards model adjusted for established clinical prognostic factors (i.e., age, gender, histopathology, depth of invasion, lymph node involvement). The combination of RKIP and p-ERK expression was found to be an independent prognostic factor (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3 - 4.6; p = 0.008). Histopathological type and depth of invasion were also independent prognostic factors (HR, 2.1; 95% CI, 1.0 - 4.2; p = 0.043 and HR, 4.7; 95% CI, 1.0-22; p = 0.048, respectively) (Table 3).

Bottom Line: Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively.RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79).Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

ABSTRACT

Background: The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor protein (RKIP), and investigated correlations of these expressions with clinicopathological features and outcomes in gastric cancer.

Methods: Tumour samples were obtained from 105 patients with gastric adenocarcinomas who underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK), phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical staining.

Results: Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively correlated with the depth of invasion (p < 0.001), lymph node involvement (p = 0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression had slightly, but not significantly shorter RFS than those without such expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001). The combination of RKIP and p-ERK expression was an independent prognostic factor (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008).

Conclusions: Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival. Negative RKIP expression combined with positive p-ERK expression was an independent predictor of poor outcomes in patients with gastric cancer.

Show MeSH
Related in: MedlinePlus