Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer

by Selleckchem | Nov 05 2023

Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer globally, and its treatment remains a significant challenge. Therefore, it is crucial to comprehend the microenvironment to improve therapy and prognosis urgently. In this study, we utilized bioinformatic methods to analyze the transcription expression profile of patient samples with complete clinical information from the TCGA-LUAD datasets. To validate our findings, we also analyzed the Gene Expression Omnibus (GEO) datasets. The super-enhancer (SE) was visualized using the peaks of the H3K27ac and H3K4me1 ChIP-seq signal, which were identified by the Integrative Genomics Viewer (IGV). To further investigate the role of Centromere protein O (CENPO) in LUAD, we conducted various assays including Western blot, qRT-PCR, flow cytometry, wound healing and transwell assays to assess the cell functions of CENPO in vitro. The overexpression of CENPO is linked to a poor prognosis in patients with LUAD. Strong signal peaks of H3K27ac and H3K4me1 were also observed near the predicted SE regions of CENPO. CENPO was found to be positively associated with the expression levels of immune checkpoints and drug IC50 value (Roscovitine and TGX221), but negatively associated with the fraction levels of several immature cells and drug IC50 value (CCT018159, GSK1904529A, Lenaildomide, and PD-173074). Additionally, CENPO-associated prognostic signature (CPS) was identified as an independent risk factor. The high-risk group for LUAD is identified based on CPS enrichment, which involved not only endocytosis that transfers mitochondria to promote cell survival in response to chemotherapy but also cell cycle promotion that leads to drug resistance. The removal of CENPO significantly suppressed metastasis and induced arrest and apoptosis of LUAD cells. The involvement of CENPO in the immunosuppression of LUAD provides a prognostic signature for LUAD patients.

Comments:

This study focuses on investigating the microenvironment and the role of Centromere protein O (CENPO) in lung adenocarcinoma (LUAD). The researchers utilized bioinformatic methods to analyze the transcription expression profile of patient samples with complete clinical information from the TCGA-LUAD datasets. They also validated their findings by analyzing the Gene Expression Omnibus (GEO) datasets.

The researchers visualized the super-enhancer (SE) using the peaks of the H3K27ac and H3K4me1 ChIP-seq signal, which were identified using the Integrative Genomics Viewer (IGV). They conducted various in vitro assays, such as Western blot, qRT-PCR, flow cytometry, wound healing, and transwell assays, to assess the cell functions of CENPO.

The study found that overexpression of CENPO is associated with a poor prognosis in patients with LUAD. Strong signal peaks of H3K27ac and H3K4me1 were observed near the predicted SE regions of CENPO. CENPO was positively associated with the expression levels of immune checkpoints and drug IC50 values for Roscovitine and TGX221. On the other hand, it was negatively associated with the fraction levels of several immature cells and drug IC50 values for CCT018159, GSK1904529A, Lenalidomide, and PD-173074.

Furthermore, the researchers identified a CENPO-associated prognostic signature (CPS) as an independent risk factor. The high-risk group for LUAD was identified based on CPS enrichment, which involved endocytosis that transfers mitochondria to promote cell survival in response to chemotherapy and cell cycle promotion that leads to drug resistance.

The study also demonstrated that the removal of CENPO significantly suppressed metastasis and induced cell cycle arrest and apoptosis of LUAD cells. The involvement of CENPO in the immunosuppression of LUAD provides a prognostic signature for LUAD patients.

Overall, this research provides valuable insights into the microenvironment and the role of CENPO in LUAD, suggesting its potential as a prognostic biomarker and a therapeutic target in the treatment of this prevalent form of lung cancer.