Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma

doi:10.1186/s12935-024-03366-6

科研成果详情

题名	Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma
作者	Mao, Xiaomin 1; Xu, Shumin 2; Wang, Huan 2; Xiao, Peng 3; Li, Shumin4; Wu, Jiaji 2; Sun, Junhui5; Jin, Cheng 6; Shen, Mo 2; Shi, Yueli 2; Tang, Bufu 3; Yang, Ying 2; Chen, Weiyu 2; Xu, Zhiyong 2; Xu, Yun 2
发表日期	2024-05-17
发表期刊	Cancer Cell International 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Cisplatin resistance E2F7 Immune infiltration Lung adenocarcinoma Prognostic
其他关键词	CELL-PROLIFERATION ; CANCER ; FAM83A ; IMMUNOTHERAPY ; MIGRATION
摘要	Drug resistance poses a significant challenge in cancer treatment, particularly as a leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, the development of resistance against cisplatin is a major obstacle. Therefore, identifying genes resistant to cisplatin and adopting personalized treatment could significantly improve patient outcomes., By examining transcriptome data of cisplatin-resistant LUAD cells from the GEO database, 181 genes associated with cisplatin resistance were identified. Using univariate regression analysis, random forest and multivariate regression analyses, two prognostic genes, E2F7 and FAM83A, were identified. This study developed a prognostic model utilizing E2F7 and FAM83A as key indicators. The Cell Counting Kit 8 assay, Transwell assay, and flow cytometry were used to detect the effects of E2F7 on the proliferation, migration, invasiveness and apoptosis of A549/PC9 cells. Western blotting was used to determine the effect of E2F7 on AKT/mTOR signaling pathway., This study has pinpointed two crucial genes associated with cisplatin resistance, E2F7 and FAM83A, and developed a comprehensive model to assist in the diagnosis, prognosis, and evaluation of relapse risk in LUAD. Analysis revealed that patients at higher risk, according to these genetic markers, had elevated levels of immune checkpoints (PD-L1 and PD-L2). The prognostic and diagnosis values of E2F7 and FAM83A were further confirmed in clinical data. Furthermore, inhibiting E2F7 in lung cancer cells markedly reduced their proliferation, migration, invasion, and increased apoptosis. In vivo experiments corroborated these findings, showing reduced tumor growth and lung metastasis upon E2F7 suppression in lung cancer models., Our study affirms the prognostic value of a model based on two DEGs, offering a reliable method for predicting the success of tumor immunotherapy in patients with LUAD. The diagnostic and predictive model based on these genes demonstrates excellent performance. In vitro, reducing E2F7 levels shows antitumor effects by blocking LUAD growth and progression. Further investigation into the molecular mechanisms has highlighted E2F7's effect on the AKT/mTOR signaling pathway, underscoring its therapeutic potential. In the era of personalized medicine, this DEG-based model promises to guide clinical practice.
资助项目	China Postdoctoral Science Foundation[2021M692799];Zhejiang Provincial Natural Science Foundation of China[LQ22H010002];Natural Science Foundation of Jiangsu Province[BK20230190];National Natural Science Foundation of China[82102852,82100029];Yiwu Science and Technology Bureau[20–3-214];Medical Scientific Research Foundation of Zhejiang Province[2021RC087];Top Talent Support Program for young and middle-aged people of Wuxi Health Committee[BJ2023098];
出版者	BMC
ISSN	1475-2867
EISSN	1475-2867
卷号	24 期号:1
DOI	10.1186/s12935-024-03366-6
页数	19
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:001227059900001
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	38760774
SCOPUSEID	2-s2.0-85193504738
通讯作者地址	[Chen, Weiyu]Department of Respiratory and Critical Care Medicine,Center for Oncology Medicine,the Fourth Affiliated Hospital of School of Medicine,and International School of Medicine,International Institutes of Medicine,Zhejiang University,Yiwu,322000,China ; [Xu, Zhiyong]Department of Respiratory and Critical Care Medicine,Center for Oncology Medicine,the Fourth Affiliated Hospital of School of Medicine,and International School of Medicine,International Institutes of Medicine,Zhejiang University,Yiwu,322000,China ; [Xu, Yun]Department of Respiratory and Critical Care Medicine,Center for Oncology Medicine,the Fourth Affiliated Hospital of School of Medicine,and International School of Medicine,International Institutes of Medicine,Zhejiang University,Yiwu,322000,China
Scopus学科分类	Oncology;Genetics;Cancer Research
SCOPUS_ID	SCOPUS_ID:85193504738
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/212909
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院附属第一医院_生殖医学中心
通讯作者	Chen, Weiyu; Xu, Zhiyong; Xu, Yun
作者单位	1.Department of Nursing,The Fourth Affiliated Hospital,Zhejiang University School of Medicine,Zhejiang University,Yiwu,322000,China; 2.Department of Respiratory and Critical Care Medicine,Center for Oncology Medicine,the Fourth Affiliated Hospital of School of Medicine,and International School of Medicine,International Institutes of Medicine,Zhejiang University,Yiwu,322000,China; 3.School of Medicine,Zhejiang University,Hangzhou,310058,China; 4.Department of Respiratory and Critical Care Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China; 5.Department of Reproductive Medicine Center,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China; 6.Wuxi Center for Disease Control and Prevention,The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University,Wuxi,214023,China
推荐引用方式 GB/T 7714	Mao, Xiaomin,Xu, Shumin,Wang, Huan,et al. Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma[J]. Cancer Cell International,2024,24(1).
APA	Mao, Xiaomin., Xu, Shumin., Wang, Huan., Xiao, Peng., Li, Shumin., ... & Xu, Yun. (2024). Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma. Cancer Cell International, 24(1).
MLA	Mao, Xiaomin,et al."Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma".Cancer Cell International 24.1(2024).