Limits...
Stage-specific prognostic biomarkers in melanoma.

Cheng Y, Lu J, Chen G, Ardekani GS, Rotte A, Martinka M, Xu X, McElwee KJ, Zhang G, Zhou Y - Oncotarget (2015)

Bottom Line: Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression.We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients).Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test).

View Article: PubMed Central - PubMed

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

ABSTRACT
The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression. Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients). Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities.

No MeSH data available.


Related in: MedlinePlus

5-Year Kaplan-Meier survival analyses for emerged stage-specific biomarkers in expanded population of melanoma patients(a) Strong BRAF expression significantly correlates with worse 5-year survival in AJCC Stage I patients (73 patients, P = 0.010, Log-rank test). (b) Strong MMP2 expression significantly correlates with worse 5-year survival in AJCC Stage II patients (123 patients, P < 0.001, Log-rank test). (c) Strong cytoplasm p27 expression significantly correlates with worse 5-year survival in AJCC Stage III patients (95 patients, P = 0.018, Log-rank test). (d) Strong cytoplasm p27 expression significantly correlates with worse 5-year survival in AJCC Stage IV patients (49 patients, P = 0.046, Log-rank test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4414181&req=5

Figure 2: 5-Year Kaplan-Meier survival analyses for emerged stage-specific biomarkers in expanded population of melanoma patients(a) Strong BRAF expression significantly correlates with worse 5-year survival in AJCC Stage I patients (73 patients, P = 0.010, Log-rank test). (b) Strong MMP2 expression significantly correlates with worse 5-year survival in AJCC Stage II patients (123 patients, P < 0.001, Log-rank test). (c) Strong cytoplasm p27 expression significantly correlates with worse 5-year survival in AJCC Stage III patients (95 patients, P = 0.018, Log-rank test). (d) Strong cytoplasm p27 expression significantly correlates with worse 5-year survival in AJCC Stage IV patients (49 patients, P = 0.046, Log-rank test).

Mentions: To confirm the prognostic value of each stage-specific marker, we performed additional analyses in an additional cohort of patients, as well as a combined cohort (discovery plus additional). Because BRAF expression emerged as the strongest biomarker for Stage I melanoma in the discovery phase, we performed both survival and multivariate Cox-regression analyses based on 73 Stage I patients (analysis was not executed in additional patients, because none of the 18 patients died; Table 4). As shown in Table 5, BRAF possesses a hazard ratio of 4.48 and a P value of 0.049 (95% CI: 1.01–19.91). Not surprisingly, 93.2% of patients with weak BRAF expression survived, as compared to 69.2% of those with strong BRAF expression who survived, for at least 5 years (P = 0.010, Log-rank test) (Figure 2a).


Stage-specific prognostic biomarkers in melanoma.

Cheng Y, Lu J, Chen G, Ardekani GS, Rotte A, Martinka M, Xu X, McElwee KJ, Zhang G, Zhou Y - Oncotarget (2015)

5-Year Kaplan-Meier survival analyses for emerged stage-specific biomarkers in expanded population of melanoma patients(a) Strong BRAF expression significantly correlates with worse 5-year survival in AJCC Stage I patients (73 patients, P = 0.010, Log-rank test). (b) Strong MMP2 expression significantly correlates with worse 5-year survival in AJCC Stage II patients (123 patients, P < 0.001, Log-rank test). (c) Strong cytoplasm p27 expression significantly correlates with worse 5-year survival in AJCC Stage III patients (95 patients, P = 0.018, Log-rank test). (d) Strong cytoplasm p27 expression significantly correlates with worse 5-year survival in AJCC Stage IV patients (49 patients, P = 0.046, Log-rank test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414181&req=5

Figure 2: 5-Year Kaplan-Meier survival analyses for emerged stage-specific biomarkers in expanded population of melanoma patients(a) Strong BRAF expression significantly correlates with worse 5-year survival in AJCC Stage I patients (73 patients, P = 0.010, Log-rank test). (b) Strong MMP2 expression significantly correlates with worse 5-year survival in AJCC Stage II patients (123 patients, P < 0.001, Log-rank test). (c) Strong cytoplasm p27 expression significantly correlates with worse 5-year survival in AJCC Stage III patients (95 patients, P = 0.018, Log-rank test). (d) Strong cytoplasm p27 expression significantly correlates with worse 5-year survival in AJCC Stage IV patients (49 patients, P = 0.046, Log-rank test).
Mentions: To confirm the prognostic value of each stage-specific marker, we performed additional analyses in an additional cohort of patients, as well as a combined cohort (discovery plus additional). Because BRAF expression emerged as the strongest biomarker for Stage I melanoma in the discovery phase, we performed both survival and multivariate Cox-regression analyses based on 73 Stage I patients (analysis was not executed in additional patients, because none of the 18 patients died; Table 4). As shown in Table 5, BRAF possesses a hazard ratio of 4.48 and a P value of 0.049 (95% CI: 1.01–19.91). Not surprisingly, 93.2% of patients with weak BRAF expression survived, as compared to 69.2% of those with strong BRAF expression who survived, for at least 5 years (P = 0.010, Log-rank test) (Figure 2a).

Bottom Line: Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression.We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients).Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test).

View Article: PubMed Central - PubMed

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

ABSTRACT
The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression. Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients). Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities.

No MeSH data available.


Related in: MedlinePlus