Identification and validation of L Antigen Family Member 3 as an immune-related biomarker associated with the progression of papillary thyroid cancer

Abstract Background Papillary thyroid cancer (PTC) is heterogeneous cancer with many different immune cells involved in its pathogenesis. L Antigen Family Member 3 (LAGE3) is an ESO/LAGE gene family member that has not been extensively studied in PTC. Methods Comprehensive bioinformatics analyses of LAGE3 were based on The Cancer Genome Atlas, Gene Expression Omnibus, and Genomics of Drug Sensitivity in Cancer (GDSC) databases. We also performed RNA-sequencing on 78 paired samples from local PTC patients. Results We observed that LAGE3 was significantly up-regulated in most solid tumor types, including PTC compared with corresponding normal tissues. The high level of LAGE3 was also significantly associated with advanced malignancy. LAGE3 expression was significantly associated with cancer-related pathways, biochemical metabolism, and immune-related terms. Further, tumor microenvironment analysis indicated LAGE3 was positively correlated with different immune cells infiltrating levels and the activity of different steps of the cancer-immunity cycle. Analyses based on the GDSC database revealed that low levels of LAGE3 might be resistant to WZ3105, I-BET-762, and PHA-793887. In addition, the experimental results validated that knocking down LAGE3 could affect proliferation, migration, and invasion in the PTC cell lines. Conclusion This study discloses that LAGE3 plays an oncogenic and cancer-immunological role, also providing novel PTC biological and clinical implications.