To further uncover the underlying mechanism of PLOD3 in PLOD3, we compared the COAD samples of high PLOD3 expression with those of low PLOD3 expression and found that high expression of PLOD3 was associated with reduced expression of immune regulators and enhanced activities of two tumor-promoting pathways, including gluconeogenesis and TGF-beta signaling in epithelial-mesenchymal transition (EMT), suggesting that high expression of PLOD3 causes poor prognosis in COAD by weakening the immune cell infiltration and enhancing activities of tumor-promoting pathways. Here, PLOD3 is linked to colon adenocarcinoma.