LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches
Abstract
The present study aimed to investigate the role and expression of large tumor suppressor kinase 2 (LATS2) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The expression levels of LATS2 in LUAD and LUSC, as well as their association with clinical characteristics and patient survival, were analyzed using data obtained from The Cancer Genome Atlas. A total of 100 LATS2-related genes were screened to conduct Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses. The association between LATS2 expression and immune cell infiltration, particularly CD4<sup>+</sup> and CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs), was analyzed. The role of LATS2 in tumor cells was validated by observing the changes in proliferation, apoptosis, migration and invasion of LUAD and LUSC cells following LATS2 overexpression. LATS2 expression was low in both LUAD and LUSC. In LUAD, high expression of LATS2 was associated with lymph node metastasis, distant metastasis and TNM stage and served as an independent risk factor for both overall survival and progression-free survival. Conversely, in LUSC, LATS2 exhibited a weak association with clinical characteristics and survival. In LUAD and LUSC, LATS2-related genes exhibited differences in their associated functional pathways and biological processes. In LUAD, LATS2 was positively associated with CD4<sup>+</sup> TIL proportions and CD4<sup>+</sup>/CD8<sup>+</sup> TIL proportions, while exhibiting a negative association with CD8<sup>+</sup> TIL proportions. In LUSC, no such associations were observed. <i>In vitro</i> experiments demonstrated that overexpression of LATS2 inhibited proliferation, migration and invasion, while promoting apoptosis, in both LUAD and LUSC cell lines, with notably stronger effects observed in LUAD cells. In conclusion, LATS2 exerts tumor-suppressive functions in both LUAD and LUSC. In LUAD, LATS2 is an independent risk factor for patient survival, possibly due to its close association with CD8<sup>+</sup> TIL levels; however, this relationship is not pronounced in LUSC.