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Cytoplasmic Skp2 expression is increased in human melanoma and correlated with patient survival.

Chen G, Cheng Y, Zhang Z, Martinka M, Li G - PLoS ONE (2011)

Bottom Line: Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival.The univariate and multivariate Cox regression models were performed to estimate the hazard ratios (HR) at five-year follow-up.Cytoplasmic Skp2 expression correlated with AJCC stages (I vs II-IV, P<0.001), tumor thickness (≤2.00 vs >2.00 mm, P<0.001) and ulceration (P = 0.005).

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

ABSTRACT

Background: S-phase kinase protein 2 (Skp2), an F-box protein, targets cell cycle regulators via ubiquitin-mediated degradation. Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival. In melanoma, however, the prognostic significance of subcellular Skp2 expression remains controversial.

Methods: To investigate the role of Skp2 in melanoma development, we constructed tissue microarrays and examined Skp2 expression in melanocytic lesions at different stages, including 30 normal nevi, 61 dysplastic nevi, 290 primary melanomas and 146 metastatic melanomas. The TMA was assessed for cytoplasmic and nuclear Skp2 expression by immunohistochemistry. The Kaplan-Meier method was used to evaluate the patient survival. The univariate and multivariate Cox regression models were performed to estimate the hazard ratios (HR) at five-year follow-up.

Results: Cytoplasmic but not nuclear Skp2 expression was gradually increased from normal nevi, dysplastic nevi, primary melanomas to metastatic melanomas. Cytoplasmic Skp2 expression correlated with AJCC stages (I vs II-IV, P<0.001), tumor thickness (≤2.00 vs >2.00 mm, P<0.001) and ulceration (P = 0.005). Increased cytoplasmic Skp2 expression was associated with a poor five-year disease-specific survival of patients with primary melanoma (P = 0.018) but not metastatic melanoma (P>0.05).

Conclusion: This study demonstrates that cytoplasmic Skp2 plays an important role in melanoma pathogenesis and its expression correlates with patient survival. Our data indicate that cytoplasmic Skp2 may serve as a potential biomarker for melanoma progression and a therapeutic target for this disease.

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Cytoplasmic Skp2 expression is associated with five-year survival of all melanoma and primary melanoma patients.Kaplan-Meier curves analyses for the correlation between cytoplasmic Skp2 expression and overall or disease-specific five-year survival in all melanoma patients (A,B), primary melanoma patients (C,D) and metastatic melanoma patients (E,F).
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pone-0017578-g004: Cytoplasmic Skp2 expression is associated with five-year survival of all melanoma and primary melanoma patients.Kaplan-Meier curves analyses for the correlation between cytoplasmic Skp2 expression and overall or disease-specific five-year survival in all melanoma patients (A,B), primary melanoma patients (C,D) and metastatic melanoma patients (E,F).

Mentions: A total of 392 patients had complete follow-up and clinical information (Figure 1). Demographic and clinical characteristics of the patients were listed in Table 2 and Supporting Information Table S1 and S2. The Kaplan-Meier curve and log-rank test analyses revealed that increased cytoplasmic Skp2 expression was associated with poor overall (P = 0.025) or disease-specific five-year survival (P = 0.035) (Figure 4A and B). Next, we separated all melanoma (n = 392) into primary melanoma (n = 259) and metastatic melanoma (n = 133) and found cytoplasmic Skp2 expression was associated with overall (P = 0.025) and disease-specific five-year survival (P = 0.018) in primary melanoma patients (Figure 4C and D). However, cytoplasmic Skp2 expression was not associated with overall and disease-specific five-year survival in metastatic melanoma patients (P>0.05 for both) (Figure 4E and F). Since previous study showed that nuclear Skp2 expression was associated with melanoma patient survival [14], we also examined the correlation between nuclear Skp2 expression and patient survival. The results indicate that nuclear Skp2 expression is not associated with overall and disease-specific five-year survival in all melanoma, primary melanoma or metastatic melanoma patients (Supporting Information Figure S5).


Cytoplasmic Skp2 expression is increased in human melanoma and correlated with patient survival.

Chen G, Cheng Y, Zhang Z, Martinka M, Li G - PLoS ONE (2011)

Cytoplasmic Skp2 expression is associated with five-year survival of all melanoma and primary melanoma patients.Kaplan-Meier curves analyses for the correlation between cytoplasmic Skp2 expression and overall or disease-specific five-year survival in all melanoma patients (A,B), primary melanoma patients (C,D) and metastatic melanoma patients (E,F).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046256&req=5

pone-0017578-g004: Cytoplasmic Skp2 expression is associated with five-year survival of all melanoma and primary melanoma patients.Kaplan-Meier curves analyses for the correlation between cytoplasmic Skp2 expression and overall or disease-specific five-year survival in all melanoma patients (A,B), primary melanoma patients (C,D) and metastatic melanoma patients (E,F).
Mentions: A total of 392 patients had complete follow-up and clinical information (Figure 1). Demographic and clinical characteristics of the patients were listed in Table 2 and Supporting Information Table S1 and S2. The Kaplan-Meier curve and log-rank test analyses revealed that increased cytoplasmic Skp2 expression was associated with poor overall (P = 0.025) or disease-specific five-year survival (P = 0.035) (Figure 4A and B). Next, we separated all melanoma (n = 392) into primary melanoma (n = 259) and metastatic melanoma (n = 133) and found cytoplasmic Skp2 expression was associated with overall (P = 0.025) and disease-specific five-year survival (P = 0.018) in primary melanoma patients (Figure 4C and D). However, cytoplasmic Skp2 expression was not associated with overall and disease-specific five-year survival in metastatic melanoma patients (P>0.05 for both) (Figure 4E and F). Since previous study showed that nuclear Skp2 expression was associated with melanoma patient survival [14], we also examined the correlation between nuclear Skp2 expression and patient survival. The results indicate that nuclear Skp2 expression is not associated with overall and disease-specific five-year survival in all melanoma, primary melanoma or metastatic melanoma patients (Supporting Information Figure S5).

Bottom Line: Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival.The univariate and multivariate Cox regression models were performed to estimate the hazard ratios (HR) at five-year follow-up.Cytoplasmic Skp2 expression correlated with AJCC stages (I vs II-IV, P<0.001), tumor thickness (≤2.00 vs >2.00 mm, P<0.001) and ulceration (P = 0.005).

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

ABSTRACT

Background: S-phase kinase protein 2 (Skp2), an F-box protein, targets cell cycle regulators via ubiquitin-mediated degradation. Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival. In melanoma, however, the prognostic significance of subcellular Skp2 expression remains controversial.

Methods: To investigate the role of Skp2 in melanoma development, we constructed tissue microarrays and examined Skp2 expression in melanocytic lesions at different stages, including 30 normal nevi, 61 dysplastic nevi, 290 primary melanomas and 146 metastatic melanomas. The TMA was assessed for cytoplasmic and nuclear Skp2 expression by immunohistochemistry. The Kaplan-Meier method was used to evaluate the patient survival. The univariate and multivariate Cox regression models were performed to estimate the hazard ratios (HR) at five-year follow-up.

Results: Cytoplasmic but not nuclear Skp2 expression was gradually increased from normal nevi, dysplastic nevi, primary melanomas to metastatic melanomas. Cytoplasmic Skp2 expression correlated with AJCC stages (I vs II-IV, P<0.001), tumor thickness (≤2.00 vs >2.00 mm, P<0.001) and ulceration (P = 0.005). Increased cytoplasmic Skp2 expression was associated with a poor five-year disease-specific survival of patients with primary melanoma (P = 0.018) but not metastatic melanoma (P>0.05).

Conclusion: This study demonstrates that cytoplasmic Skp2 plays an important role in melanoma pathogenesis and its expression correlates with patient survival. Our data indicate that cytoplasmic Skp2 may serve as a potential biomarker for melanoma progression and a therapeutic target for this disease.

Show MeSH
Related in: MedlinePlus