Insulin-Like Growth Factor-1 as a Predictive Biomarker for Metastatic Uveal Melanoma in Humans

Abstract

PURPOSE. High expression levels of insulin-like growth factor-1 (IGF-1) receptor were associated with metastatic uveal melanoma (UM). The purpose of this study was to examine the potential of serum IGF-1 in early detection of liver metastasis.METHODS. IGF-1 serum levels were analyzed using enzymelinked immunosorbent assay for 118 subjects in three different groups: 55 disease-free (DF) UM patients who did not develop metastasis within 10 years of diagnosis; 22 metastatic patients; and 41 healthy subjects. Matched pairs univariate analysis was performed for sera of 19 metastatic patients 12 and 6 months before the diagnosis of metastasis and on the day of diagnosis, both as time groups and normalized levels per patient. IGF-1 levels were compared among groups by analysis of variance and Student t-test. RESULTS.Mean 6 SD IGF-1 serum levels for the control, DF, and metastatic groups were 152.48 6 49.76, 119.92 6 60.66, and 96.99 6 56.91 ng/mL, respectively (P < 0.001). Normalized changes in IGF-1 per metastatic patient from 6 months prior to the diagnosis of metastases compared to the day of diagnosis of metastases showed a decreasing trend.CONCLUSIONS. IGF-1 levels in 10-years' disease-free UM patients were significantly lower than those in healthy subjects and were even lower in metastatic patients. IGF-1 levels decreased toward the diagnosis of metastases. Therefore, serum IGF-1 level may be used as a predictive biomarker for metastatic UM when measured repeatedly. (Invest Ophthalmol Vis Sci. 2013; 54:490-493) DOI:10.1167/iovs.12-10228 U veal melanoma (UM) is the most common primary intraocular malignant tumor in adults, 1 albeit a rare tumor with a mean age-adjusted incidence in the United States of 5.1 per million, representing only 3.1% of all recorded cases of melanoma.2 The liver is the predominant metastatic organ, and in the collaborative ocular melanoma study (COMS), the liver was involved in 89% of cases. 3Brachytherapy and external irradiation (proton beam, stereotactic radiosurgery, or gamma knife) are the most common treatment options for small-to medium-sized tumors, with a success rate of approximately 90%, while enucleation remains the common treatment for large tumors. Despite the high success rate in treating the primary tumors, the 5-and 10-year cumulative rates for developing metastases are 25% and 34%, respectively, with 80% of the metastatic patients dying within 1 year and 92% within 2 years of the diagnosis of metastases. 4 However, metastases have been diagnosed even more than 40 years from enucleation.5 These findings led to the hypothesis that micrometastases had already been seeded at the time of diagnosis and developed over time as a result of unknown factors until metastatic disease was diagnosed. 6 Currently there is no adjuvant chemotherapy to eliminate micrometastases, and treatments for overt metastatic disease are of limited value except for a subgroup of patients who are diagnosed early enough to allow complete surgical resection of liver metastases. 7,8 Liver resection may inc...

Serum adiponectin, insulin resistance, and uveal melanoma

“…Multiple studies have reported overexpression of IGF-1 receptors in various cancers, including uveal melanoma; therefore, the effects of insulin on cancer cell Sensitivity proliferation in vivo are believed to be indirectly related to IGF-1 production, which has proliferative and antiapoptotic effects and increases the levels of VEGF by upregulating growth hormone receptors in the liver and by decreasing insulin-binding proteins [8,12,21]. In uveal melanoma, IGF-1-receptor positive tumor cell ratios have been associated with a poor prognosis [22], and serum IGF-1 levels were found to be related to scleral invasion [12] and liver metastasis [8]. Osteopontin, S100b, melanoma-inhibiting antigen, VEGF, and DJ-1 were also shown to be the increased parameters identified in metastatic disease [8].…”

“…Currently, the method for detecting metastasis is a combination of blood tests with abdominal imaging. However, neither the currently available serum biomarkers nor the imaging methods provide a long enough lead time for a complete surgical resection of the liver metastasis to be performed [8]. Thus, it is very important to find reliable serum biomarkers to identify the patients at high risk for the development of metastasis.…”

“…Serum levels of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) have been shown to be related to the prognosis of uveal melanoma in several studies [8,12]. Both IGF-1 and VEGF are strongly related to insulin resistance and metabolic syndrome.…”

Ocular oncology: advances in retinoblastoma, uveal melanoma and conjunctival melanoma

“…The authors concluded that serial IGF-1 levels may have a role as a predictive biomarker for metastatic uveal melanoma when measured repeatedly in one individual. 49 Triozzi et al studied 76 treated primary uveal melanoma patients and found a correlation between the presence of monosomy 3 and human leukocyte antigen-class-I-associated β-2 microglobulin (P≤0.02). Based on the strong association between monosomy 3 and development of metastatic disease, the authors concluded that the microglobulin may have a potential role as a screening tool for metastatic disease.…”

The Role of Pathologic and Molecular Genetic Factors in Development of Uveal Melanoma Extrabulbar Growth

“…The molecular prognostic factors comprise the presence of mRNA tyrosinase, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (ILGF-1) [12][13][14][15]. The risk factors of the chromosome aberration and gene mutations refer to the loss of one copy of chromosome 3 (monosomy), doubling of chromosome 8, mutation in GNAQ and GNA11 genes, СС genotype of polymorphic C3435T marker of ABCB1 gene and a number of other changes [3,10,[16][17][18][19].…”