Inhibition of O-GalNAc glycosylation or knockdown of Galnt9 demonstrates efficacy in restraining the liver metastasis of NEPC, small cell lung cancer (SCLC), and colorectal neuroendocrine cancer. These findings identify Galnt9-mediated O-GalNAc glycosylation as a targetable mechanism driving liver metastasis through activation of MBL complement and coagulation cascades across a broad spectrum of NE cancers.
Overall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.
An additional seven genes (VARS1, ZBED9, PRRC2A, VWA7, TRIM31, TRIM40, and COL8A2) were associated with a Middle Eastern PTC risk based on the sequence kernel association test (SKAT). This study underscores the potential of GALNT9 and other implicated genes in PTC predisposition, illuminating the need for large collaborations and innovative approaches to understand the genetic heterogeneity of PTC predisposition.