Comprehensive pan-cancer analysis of CHRDL1 and experimental validation of its role in lung adenocarcinoma

Chordin-like 1 (CHRDL1) is a secreted antagonist of bone morphogenetic proteins, and has been implicated in various biological processes and cancer prognosis. This study offered a detailed examination of CHRDL1 expression across 33 diverse cancer types, leveraging data from The Cancer Genome Atlas (TCGA) and supplementary public datasets. We demonstrated that, for the majority of cancer types, CHRDL1 expression was reduced in tumor tissues compared to normal adjacent tissues. Notably, lower CHRDL1 expression led to negative prognosis in malignancies such as lung adenocarcinoma (LUAD), melanoma (SKCM), and mesothelioma (MESO). Furthermore, CHRDL1 expression was positively correlated with the infiltration of CD4⁺ T cells, CD8⁺ T cells, B cells, neutrophils, macrophages, and dendritic cells in most tumors. Higher CHRDL1 expression correlated with more favorable immune profiles and a reduction in tumor stemness. To assess the effect of CHRDL1 overexpression on LUAD progression, we conducted CCK-8, wound healing, and invasion assays in vitro, along with subcutaneous tumor formation experiments in nude mice. The results showed that the proliferation, migration, and invasion abilities of A549 and H1299 cells with high CHRDL1 expression were reduced, and the growth of A549 cells was also significantly inhibited in nude mice. These findings underscored CHRDL1's potential as a prognostic biomarker and its influence on tumor immunology and cellular dynamics.