Insulin-Like Growth Factor II mRNA-Binding Protein 3 Expression Correlates with Poor Prognosis in Acral Lentiginous Melanoma.

Yi-Shuan Sheen,Chia-Yu Chu,Jau-Yu Liau,Yi-Hua Liao,Shiou-Hwa Jee,Ming-Hsien Lin,Yih-Leong Chang,Hsien-Ching Chiu,Andrzej T Slominski

doi:10.1371/journal.pone.0147431

Yi-Shuan Sheen, Chia-Yu Chu + Show 7 more

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https://doi.org/10.1371/journal.pone.0147431

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Abstract

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is an RNA-binding protein expressed in multiple cancers, including melanomas. However, the expression of IMP-3 has not been investigated in acral lentiginous melanoma (ALM). This study sought to elucidate its prognostic value in ALMs. IMP-3 expression was studied in 93 patients diagnosed with ALM via immunohistochemistry. Univariate and multivariate analyses for survival were performed, according to clinical and histologic parameters, using the Cox proportional hazard model. Survival curves were graphed using the Kaplan-Meier method. IMP-3 was over-expressed in 70 out of 93 tumors (75.3%). IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (P = 0.002, 0.006, 0.008 and 0.012, respectively). Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (P = 0.048). IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35–9.97, P = 0.011) was confirmed to be an independent prognostic factor for melanoma-specific survival in multivariate survival analysis. Positive IMP-3 expression was an important prognostic factor for ALMs.

Highlights

Insulin-like growth factor II mRNA-binding protein 3 (IMP-3) is expressed in fetal tissues in a time-dependent and cell-dependent manner, but it is undetectable in human adult tissues [1, 2]
IMP-3 expression in acral lentiginous melanoma (ALM) tumor tissues could provide complementary prognostic information, in addition to the major clinicopathological features, which in turn could help to determine the best choice of therapy
Further mechanistic researches are warranted to work out whether IMP-3 is a therapeutic target for new modalities in the therapy of ALMs

Summary

Introduction

Insulin-like growth factor II mRNA-binding protein 3 (IMP-3) is expressed in fetal tissues in a time-dependent and cell-dependent manner, but it is undetectable in human adult tissues [1, 2]. IMP-3 appears to play an important role in the differentiation process of embryogenesis [3]. IMP-3 was shown to promote proliferation of human leukemia cells and invasion of hepatocellular carcinoma [1, 3]. Evidence from an in vitro IMP-3 knockdown research and from IMP-3 administration in lung cancer patients illustrated that IMP-3 may be a therapeutic target for malignancies [1]. Increased IMP-3 expression was described in carcinomas of the colon, kidney and liver, as well as in melanomas [3,4,5,6,7].

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