microRNA-10b is a prognostic biomarker for melanoma

Abstract

Malignant melanoma is an aggressive form of skin cancer. Recently, drug therapy of advanced disease has been revolutionized by new agents. More therapeutic options, coupled with the desire to extend treatment to the adjuvant setting mean that prognostic biomarkers that can be assayed from formalin-fixed paraffin-embedded clinical would be valuable. microRNAs have potential to fill this need. We analyzed 377 microRNAs in 79 primary melanomas and 32 metastases using a split sample discovery strategy. From a discovery analysis using 40 thick primary melanomas (20 cases with metastasis and 20 controls without metastasis at 5 years), microRNA expression was measured by quantitative RT-PCR (QRT-PCR). MiR-10b emerged as a candidate prognostic microRNA. This was confirmed in an independent validation set of thick primary melanomas (20 cases with metastasis and 19 controls without metastasis at 5 years). In the combined discovery and validation cohorts (n = 79), miR-10b expression showed a 3.7-fold increase in expression between cases and controls (P = 0.005) and showed a trend of increasing expression between primary melanomas and their matched metastases (Po 0.001). In situ hybridization showed expression was in melanoma cells and correlated with expression measured by QRT-PCR (P = 0.0005). We used the combined discovery and validation samples to verify the prognostic value of additional candidate microRNAs identified from other studies, and proceeded to analyze miR-200b. We demonstrated that miR-10b and miR-200b showed independent prognostic value (P = 0.002 and 0.047, respectively) in multivariable analysis alongside known clinico-pathological prognostic features (eg, Breslow thickness) using a Cox proportional hazards regression model. Furthermore, the addition of these microRNAs to the clinico-pathological features led to an improved regression model with better identification of aggressive thick melanomas. Taken together, these data suggest that miR-10b is a new prognostic microRNA for melanoma and that there could be a place for microRNA analysis in stratifying melanoma for therapy.

Several microRNAs could predict survival in patients with hepatitis B-related liver cancer

“…reported that miR-9 was overexpressed in lung cancer tissues compared with peripheral normal tissues24, similar to our results. Studies2526 have shown that miR-10b is a prognostic biomarker for melanoma and esophageal squamous cell carcinoma, similar to our conclusion. However, miR-31 expression correlated with a better outcome in advanced stage serous ovarian tumors27.…”

MicroRNAs in cutaneous melanoma: Role as diagnostic and prognostic biomarkers

“…miR‐382 and miR‐516b demonstrated decreased expression in aggressive versus in non‐aggressive primary melanomas (Hanniford et al, ). miR‐10b expression showed a 3.7‐fold increase in expression in metastatic patients compared to non‐metastatic patients at 5 years (Saldanha et al, ). miR‐17‐92 , which is overexpressed in melanoma cell lines, was expressed twice as much in metastatic cell lines compared to primary melanoma cell lines (Mueller, Rehli, & Bosserhoff, ).…”

Streamlining Molecular Pathobiology of Malignant Melanoma

“…Gene microarrays target RNA and microRNA (miRNA) expression [49]. They also scrutinize DNA mutations and polymorphism [56,57].…”

“…The CGH method is performed using fresh or formalin-fixed tissue [42,49]. The DNA labeled with fluorochromes is next hybridized on normal metaphase chromosomes or on arrays of small spots of DNA.…”