Mega-analysis revealed that three LA-associated genes, such as solute carrier family 2 member 1 (SLC2A1), endothelial PAS domain protein 1 (EPAS1) and cyclin-dependent kinase 4 (CDK4), were significantly associated with LSCC (P<1.60×10<sup>-8</sup>), with multiple potential pathways identified by functional pathway analysis, which were further validated by co-expression analysis.
In vivo PDK4 expression was elevated in a Cisplatin-resistant population of lung adenocarcinoma cells, PDK4-dependent Cisplatin-resistance promotes tumor growth of lung adenocarcinoma in vivo and in vitro, clinically PDK4 expression was associated with poor prognosis in lung adenocarcinoma patients, mechanically PDK4 promoted cell growth and Cisplatin-resistance of lung adenocarcinoma via transcriptional regulation of endothelial PAS domain-containing protein 1 (EPAS1).
Moreover, HIF-2α expression was linked to a good survival benefit in some cancers (B-cell lymphoma and lung adenocarcinoma: OS, multiple myeloma: DSS, breast cancer: distant metastasis-free survival, liposarcoma: distant recurrence-free survival) (all HRs < 1, Ps < 0.05).