Expression and prognostic potential of osteopontin splice variants in malignant melanoma

We read with great interest the article recently published by Koroknai et al.¹ entitled “Expression pattern of osteopontin isoforms in malignant melanoma cell lines,” in which the expression of five OPN splice variants (OPN-SV) has been described in melanoma cell lines, providing new insights into this previously underexplored issue regarding osteopontin in melanoma research.

The authors found that the five OPN-SV presented higher expression levels in melanoma metastasis (MM) compared with melanoma primary (MP)-derived cell lines, although they did not reach statistical significance. They also observed that MM cell lines significantly express higher levels of all five OPN-SV in relation to those derived from primary superficial spreading melanoma (SSM), and between SSM and nodular melanoma (NM)-derived cell lines. These findings corroborate previous ones from the same group, in which OPNa, OPNb, and OPNc are expressed at higher levels in metastatic tumor tissues compared with primary lesions.² However, the recently described OPN4 and OPN5 variants presented low expression levels in both metastatic and primary tumor tissue samples, as opposed to data found in melanoma cell lines. The authors emphasized the association of OPNc at higher levels with invasive behavior. Consistent with these data, Jambor et al.² reported a significant positive correlation between OPNc expression and the presence of metastasis.

Building upon these findings, we further explored these data by analyzing skin cutaneous melanoma (SKCM) samples using the TSVdb database (http://www.tsvdb.com/). We found that metastatic SKCM samples significantly express higher levels of these five OPN-SV compared with primary melanoma tumors (Figure 1). Our data in tumor samples corroborate data regarding melanoma-derived cell lines for the five OPN-SV reported by Koroknai et al., in contrast to previous data showing that OPN4 and OPN5 isoforms are downregulated in melanoma subtypes.²

Altogether, these data provide evidence that not only OPNa, OPNb, and OPNc are overexpressed in metastatic melanoma tissues in comparison with primary tumors, but also OPN4 and OPN5, further evidencing that all five OPN-SV could be associated with an unfavorable prognosis in melanoma. Further research should elucidate how each OPN-SV could contribute to a worse prognosis in melanoma cancer, as reported for total osteopontin.³ The involvement of each OPN-SV in melanoma progression is key to a better understanding of this disease and for the development of new therapeutic approaches, considering their specific expression patterns and roles in each step of tumor progression.⁴

Funding for the works described was provided by the FAPERJ, CNPq, CAPES, and Healthy Ministry—Brazil.

The authors declared no competing interests for this work.