Results
Compared with NHW patients, HA patients presented with higher PSA levels (111.5 vs. 52.6 ng/mL, p = 0.02), and more advanced disease, including T4 tumors (41% vs. 14%, p = 0.01) and visceral metastases (41% vs. 16%, p = 0.04). Pathway analyses identified increased KRAS (FDR = 0.02), Hedgehog (FDR = 0.04), and NOTCH (FDR = 0.07) signaling in HA tumors. HA tumors exhibited higher expression of stem cell markers (ALDH1A1, ALDH1A2, PROM1) and immunoinhibitory genes (PDCD1LG2, FOXP3) (all p < 0.05), along with increased infiltration of M1 macrophages (0.72% vs. 0%) and natural killer (NK) cells (4.84% vs. 3.55%, all p < 0.05 and q < 0.10). HA tumors demonstrated higher expression of genes associated with drug efflux (ABCC1, ABCB1), EMT (TWIST1, MMP2), cell cycle (CCND2), apoptosis inhibition (BIRC2, XIAP), and epigenetic regulation (EP300, TET1, TET2) (all p < 0.05 and q < 0.10). Clinically, HA patients initiated therapy earlier (1 vs. 3 months, p ≤ 0.01), had a longer interval to second-line therapy (20 vs. 11 months, p < 0.05), and had shorter follow-up (23 vs. 44 months, p = 0.03).
