Unexpectedly, we found that the levels of CD9-positive EVs in purified EVs isolated from the same amount of serum by Tim4 were significantly reduced in metastatic PC and CRPC patients compared with therapy-naïve PC patients, whereas there was no statistical difference in the CD9-EV levels between RCC patients with and without metastasis (Supplementary Fig. S5). Here, TIMD4 is linked to pachyonychia congenita.