Transcriptome Profiling Identifies HMGA2 as a Biomarker of Melanoma Progression and Prognosis

Abstract

The genetic alterations contributing to melanoma pathogenesis are incompletely defined, and few independent prognostic features have been identified beyond the clinicopathological characteristics of the primary tumor. We used transcriptome profiling of 46 primary melanomas, 12 melanoma metastases, and 16 normal skin (N) samples to find genes associated with melanoma development and progression. Results were confirmed using immunohistochemistry and real-time PCR and replicated in an independent set of 330 melanomas using AQUA analysis of tissue microarray (TMA). Transcriptome profiling revealed that transcription factor HMGA2, previously unrecognized in melanoma pathogenesis, is significantly upregulated in primary melanoma and metastases (P-values=1.2 × 10−7 and 9 × 10−5) compared with N. HMGA2 overexpression is associated with BRAF/NRAS mutations (P=0.0002). Cox proportional hazard regression model and log-rank test showed that HMGA2 is independently associated with disease-free survival (hazard ratio (HR)=6.3, 95% confidence interval (CI)= 1.8–22.3, P=0.004), overall survival (OS) (stratified log-rank P=0.008), and distant metastases–free survival (HR=6.4, 95% CI=1.4–29.7, P=0.018) after adjusting for American Joint Committee on Cancer (AJCC) stage and age at diagnosis. Survival analysis in an independent replication TMA of 330 melanomas confirmed the association of HMGA2 expression with OS (P=0.0211). Our study implicates HMGA2 in melanoma progression and demonstrates that HMGA2 overexpression can serve as an independent predictor of survival in melanoma.

Downregulating HMGA2 attenuates epithelial-mesenchymal transition-induced invasion and migration in nasopharyngeal cancer cells

“…Similarly, some studies also indicated a significant association between HMGA2 expression and poor prognosis [25,29]. During EMT, tumor cells acquire more aggressive and metastatic ability.…”

IMP-3 Promotes Migration and Invasion of Melanoma Cells by Modulating the Expression of HMGA2 and Predicts Poor Prognosis in Melanoma

“…We also found that IMP-3 expression stabilized mRNA of HMGA2 in A2058 cells. Similar to IMP-3, HMGA2 is also an oncofetal protein that is typically downregulated in normal adult tissues and reactivated in various cancers (Raskin et al, 2013). IMP-3 locasomes may function as cytoplasmic safe houses that prevent microRNAdirected HMGA2 mRNA decay during tumor progression (Jonson et al, 2014).…”

“…To identify the potential targets of IMP-3, we examined the mRNA expression profile of IMP-3-overexpressed cells and identified transcripts upregulated by IMP-3 overexpression, which were previously identified to be involved in tumor progression (Tureci et al, 2002;Wang et al, 2012;Assi et al, 2013;Frewer et al, 2013;Ma et al, 2013;Raskin et al, 2013).…”

Analysis of Relative Expression of the Hmga2 Gene and Oncogenic Microrna-221 in Cytological Slides Obtained by a Fine-Needle Aspiration Biopsy of the Thyroid Nodules

“…Однако при развитии зло-качественных опухолей эпителиального происхожде-ния уровень экспрессии этих генов опять значительно повышается. Увеличение уровня экспрессии гена HMGA2 было отмечено при раке толстой кишки [5], мочевого пузыря [6], ЩЖ [7], кожи [8], яичников [9] и др.…”