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

作者全名："Shi, Tongdong; Hu, Zaoxiu; Tian, Li; Yang, Yanlong"

作者地址："[Yang, Yanlong] Kunming Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Kunming 650032, Yunnan, Peoples R China; [Shi, Tongdong; Tian, Li] Chongqing Med Univ, Dept Infect Dis, Key Lab Mol Biol Infect Dis, Minist Educ,Affiliated Hosp 2, 288 Tianwen Ave, Chongqing 401336, Peoples R China; [Hu, Zaoxiu] Kunming Med Univ, Dept Pathol, Affiliated Hosp 3, 519 Kunzhou Rd, Kunming 650118, Yunnan, Peoples R China"

通信作者："Yang, YL (通讯作者)，Kunming Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Kunming 650032, Yunnan, Peoples R China."

来源：TRANSLATIONAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001001551400001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：34

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Lung adenocarcinoma; CENPO; Cell cycle; Immune; CENPO-associated prognostic signature (CPS)

摘要："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 Ge-nomics 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."

基金机构："Joint Project of the Yunnan Provincial Department of Science and Technology-Kunming Medical University [202001AY070001-144, 202101AY070001-172]; Yunnan Provincial Department of Education [2019J1234, 2019J1282]; Doctoral Research Fund of the First Affiliated Hospital of Kunming Medical University [2018BS012]; Yunnan Fundamental Research Projects [202201AT070292]"

基金资助正文："This study was supported by grants from the Joint Project of the Yunnan Provincial Department of Science and Technology-Kunming Medical University (202001AY070001-144 and 202101AY070001-172) , Yunnan Provincial Department of Education (2019J1234 and 2019J1282) , Doctoral Research Fund of the First Affiliated Hospital of Kunming Medical University (2018BS012) , and Yunnan Fundamental Research Projects (202201AT070292) ."