Comprehensive analysis of the pituitary tumor-transforming gene (PTTG) family in lung adenocarcinoma: diagnostic, prognostic, and therapeutic implications.

OBJECTIVES

Lung adenocarcinoma (LUAD) is a prevalent form of non-small cell lung cancer with high morbidity and mortality rates. Identifying molecular markers and therapeutic targets is crucial for improving LUAD diagnosis and treatment. Pituitary tumor-transforming gene (PTTG) family members, PTTG1, PTTG2, and PTTG3P, have been linked to several malignancies; however, it is unclear how these genes relate to LUAD. The current retrospective study investigates the diagnostic, prognostic, and therapeutic importance of PTTG genes in LUAD.

METHODS

We used detailed in silico and in vitro experiments involving cell lines for experimental design.

RESULTS

Using RT-qPCR, we documented that PTTG1, PTTG2, and PTTG3P are significantly up-regulated in LUAD cell lines compared to controls, with PTTG2 showing the highest diagnostic potential (AUC = 1.0). Promoter methylation analysis revealed hypomethylation in LUAD samples, particularly for PTTG3P, further supporting its diagnostic relevance. Immunohistochemical staining confirmed overexpression of PTTG1 and PTTG2 proteins in LUAD tissue samples. The mutational analysis highlighted PTTG2 as the most frequently mutated gene within the PTTG family in LUAD samples, with mutations primarily being missense types. Survival analysis demonstrated that high expression of PTTG genes is associated with poorer overall survival, indicating their prognostic value. Gene enrichment analysis suggested that PTTG genes are involved in critical cancer-related pathways and cellular processes. Functional assays following siRNA-mediated knockdown of PTTG genes in A549 cells showed a significant reduction in cell proliferation. Lastly, drug sensitivity analysis revealed strong correlations between PTTG1/PTTG3P expression and resistance to various anticancer drugs.

CONCLUSION

The findings of the current study highlight the potential of PTTG genes as diagnostic biomarkers, prognostic indicators, and therapeutic targets in LUAD.