The observed decline in TRAIL-R3, DKK-3, and follistatin-like 1, HipAcid, Hex3Cer(d18:1/20:0) and PC.ae.C36:2 levels as MS progresses from CIS to RRMS or SPMS may hold implications for disease advancement. Here, FSTL1 is linked to in situ carcinoma.