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Sex-associated miR-4286 is related to Breslow thickness and TILs in stage II/III primary cutaneous melanoma

Reynolds, A. Z.; Corcoran, D. L.; Luo, L.; Busam, K. J.; Lezcano, C.; Amos, C.; Argibay, D.; Shen, R.; Begg, C. B.; Thomas, N. E.; Orlow, I.; Hernando, E.; Berwick, M.

2026-09-10 oncology
10.64898/2026.09.04.26362289 medRxiv
Show abstract

Sex differences in melanoma incidence and mortality are well-established. Previous work has shown that the female survival advantage can be largely explained by differences in clinico-pathologic features, such as age, Breslow thickness, ulceration, mitoses, and primary site. Here we test the hypothesis that sex-differentiated expression of micro-RNAs (miRNAs) may be associated with sex differences in melanoma pathology. In a sample of 715 AJCC stage II/III primary melanomas from the InterMEL project, we find two miRNAs (miR-361 and miR-4286) that are differentially expressed in males and females, and further find one of these (miR-4286) to be associated with both greater Breslow thickness and the presence of brisk tumor infiltrating lymphocytes (TILs). These results suggest that miR-4286 may be a candidate marker for sex differences in melanoma pathology. Functional experiments may confirm whether this relationship is causal or purely associative.

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