AUTHOR=Jámbor Krisztina , Koroknai Viktória , Kiss Tímea , Szász István , Pikó Péter , Balázs Margit 

TITLE=Gene Expression Patterns of Osteopontin Isoforms and Integrins in Malignant Melanoma

JOURNAL=Pathology and Oncology Research

VOLUME=28

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610608

DOI=10.3389/pore.2022.1610608

ISSN=1532-2807

ABSTRACT=<p>Osteopontin (OPN) is a multifunctional glycoprotein that physiologically interacts with different types of integrins. It is considered to be a possible prognostic biomarker in certain tumor types; however, various splicing isoforms exist, which have not been investigated in melanoma. We aimed to define the relative expression pattern of five <italic>OPN</italic> isoforms and clarify the prognostic significance of the splice variants in melanoma. We also aimed to investigate the expression pattern of eight integrins in the same tumors. Gene expression analyses revealed that the relative expression of <italic>OPNa, OPNb</italic>, and <italic>OPNc</italic> is significantly higher in metastatic tumors compared to primary lesions (<italic>p</italic> &lt; 0.01), whereas the expression of <italic>OPN4</italic> and <italic>OPN5</italic> was low in both. The more aggressive nodular melanomas had higher expression levels compared to the superficial spreading subtype (<italic>p</italic> ≤ 0.05). The relative expression of the eight tested integrins was low, with only the expression of <italic>ITGB3</italic> being detectable in nodular melanoma (Median<sub>log2</sub> = 1.274). A positive correlation was found between Breslow thickness and the expression of <italic>OPNc</italic> variant, whereby thicker tumors (&gt;4 mm) had significantly higher expression (<italic>p</italic> ≤ 0.05). The Breslow thickness was negatively correlated with the expression of <italic>OPN4</italic>, and similarly with <italic>ITGA2</italic>. <italic>OPNc</italic> also exhibited significant positive correlation with the presence of metastasis. Our data show that high expression of <italic>OPNa</italic>, <italic>OPNb</italic>, and especially <italic>OPNc</italic> and low expression of <italic>OPN4</italic> and <italic>ITGA2</italic> are associated with an advanced stage of tumor progression and poor prognosis in melanoma.</p>