Oncotarget

Clinical Research Papers:

Loss of tumor suppressors KAI1 and p27 identifies a unique subgroup of primary melanoma patients with poor ­­prognosis

Guohong Zhang, Yabin Cheng, Guangdi Chen, Yun Tang, Gholamreza Ardekani, Anand Rotte, Magdalena Martinka, Kevin McElwee, Xuezhu Xu, Qi Wang and Youwen Zhou _

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Oncotarget. 2015; 6:23026-23035. https://doi.org/10.18632/oncotarget.4854

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Abstract

Guohong Zhang1,2,*, Yabin Cheng1,*, Guangdi Chen3, Yun Tang1, Gholamreza Ardekani1, Anand Rotte1, Magdalena Martinka4, Kevin McElwee1, Xuezhu Xu5, Qi Wang5 and Youwen Zhou1,5,6

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

2 Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China

3 Bioelectromagnetics Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

4 Department of Pathology, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada

5 Department of Dermatology, 2nd Affiliated Hospital, Dalian Medical University, Dalian, China

6 Dermatologic Oncology Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

* These authors contributed equally to this work

Correspondence:

Youwen Zhou, email:

Qi Wang, email:

Keywords: primary melanoma, KAI1, p27, prognostic marker, subgroup

Received: February 25, 2015 Accepted: April 10, 2015 Published: July 14, 2015

Abstract

Primary melanoma, a highly aggressive malignancy, exhibits heterogeneity in biologic behaviors, clinical characteristics, metastasis potential and mortality. The present study sought to identify the molecular signatures that define a subgroup of primary melanomas with high risks of metastasis and mortality.

First, we identified the markers that best differentiated metastatic melanomas from primary melanomas by examining the expression of seven previously reported biomarkers (BRAF, Dicer, Fbw7, KAI1, MMP2, p27 and Tip60) in a training cohort consisting of 145 primary melanomas and 105 metastatic melanomas. KAI1 and p27, both tumor suppressors, emerged as best candidates. Loss of both tumor suppressors occurred in the majority (74.29%) of metastatic melanomas. Further, a subset (metastatic like, or “ML”, 33.10%) of primary melanomas also lost these two tumor suppressors. Kaplan-Meier analysis indicated that ML subgroup of primary melanoma patients had much worse 5 year survival compared with other primary melanoma patients (P = 0.002). The result was confirmed in an independent validation cohort with 92 primary melanomas (P = 0.030) and in the combined cohort with 237 melanoma patients (P = 3.00E-4). Additionally, compared to KAI1 and p27 as an individual prognostic marker, the combined signature is more closely associated with melanoma patient survival (P = 0.025, 0.264 and 0.009, respectively).

In conclusion, loss of both KAI1 and p27 defines a subgroup of primary melanoma patients with poor prognosis. This molecular signature may help in metastatic melanoma diagnosis and may provide information useful in identifying high-risk primary melanoma patients for more intensive clinical surveillance in the future.


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