PSYCH OpenIR
A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC
Lu, Guofang1,2,3; Du, Rui4; Feng, Bin1,2,5; Wang, Jianlin4; Zhang, Fengrui6; Pei, Jianming3; Wang, Yuanyong7; Shang, Yulong1,2
通讯作者Pei, Jianming(jmpei8@fmmu.edu.cn) ; Shang, Yulong(shangyul870222@163.com)
摘要Background: Tumor growth depends on tumor cells and the tumor microenvironment, which are regulated by inflammation and immune responses. However, the roles of inflammation and immune status in hepatocellular carcinoma (HCC) remain unclear. The aim of this study was to evaluate the prognostic value of an inflammatory response-related gene signature associated with immune status, which may provide insight into new treatment options for HCC patients.Materials and Methods: Differentially expressed genes associated with inflammation were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus, and the Molecular Signatures Database. An inflammation-associated prognostic gene signature was constructed and validated using TCGA and the International Cancer Genome Consortium datasets, respectively, using LASSO Cox regression analysis. Log-rank was performed to compare the overall survival of low-and high-risk score cohorts. Immune cell infiltration and immune-related functions were analyzed using single-sample gene enrichment analysis. The structures of the drugs identified by the prognostic model were predicted using PubChem. The drugs sensitivity of bleomycin, simvastatin and zoledronate detected by CCK8 colorimetric assay. The mRNA levels of 7 genes in HCC after drug treatment analyzed via qRT-PCR.Results: Inflammation-associated genes, including ITGA5, MEP1A, P2RX4, RIPK2, SLC7A1 and SRI, were identified and found to be associated with the prognosis of HCC. We further found that the high-risk patients experienced poor prognosis, which was observed to be an independent and significant risk factor for prognosis. Moreover, we observed elevated expression levels in multiple immune cell types and immune function. Lastly, we validated that bleomycin, simvastatin and zoledronate could regulate these genes in HCC.Conclusion: The inflammatory-response-associated gene signature could predict the prognosis and the immunological status of HCC patients. Additionally, bleomycin, simvastatin and zoledronate may represent potential drug candidates that could inhibit these genes. This may constitute a new approach for the treatment of HCC.
关键词inflammation-associated gene prognostic gene signature immune infiltration immune checkpoint hepatocellular carcinoma drug structure
2022
语种英语
DOI10.2147/JIR.S390113
发表期刊JOURNAL OF INFLAMMATION RESEARCH
卷号15页码:6729-6743
收录类别SCI
资助项目National Natural Science Foundation of China[82173241] ; National Natural Science Foundation of China[81871914] ; National Natural Science Foundation of China[81773072] ; Fourth Military Medical University Doctoral Science Foundation[2021D04lgf] ; Fourth Military Medical University Doctoral Science Foundation[2021D08wyy] ; Lingyun Program of Fourth Military Medical University[2019cyjhsyl]
出版者DOVE MEDICAL PRESS LTD
WOS关键词HEPATOCELLULAR-CARCINOMA ; GASTRIC-CANCER ; SURVIVAL ; PROLIFERATION ; ATEZOLIZUMAB ; BEVACIZUMAB ; CONTRIBUTES ; BLEOMYCIN ; HALLMARKS
WOS研究方向Immunology
WOS类目Immunology
WOS记录号WOS:000896645600001
资助机构National Natural Science Foundation of China ; Fourth Military Medical University Doctoral Science Foundation ; Lingyun Program of Fourth Military Medical University
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/44330
通讯作者Pei, Jianming; Shang, Yulong
作者单位1.Fourth Mil Med Univ, Xijing Hosp Digest Dis, State Key Lab Canc Biol, Xian, Peoples R China
2.Fourth Mil Med Univ, Xijing Hosp Digest Dis, Natl Clin Res Ctr Digest Dis, Xian, Peoples R China
3.Fourth Mil Med Univ, Dept Physiol & Pathophysiol, Natl Key Discipline Cell Biol, Xian, Peoples R China
4.Fourth Mil Med Univ, Tangdu Hosp, Inst Biomed Sci Pain, Xian, Peoples R China
5.Fourth Mil Med Univ, Xijing Hosp, Dept Radiat Oncol, Xian, Peoples R China
6.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
7.Fourth Mil Med Univ, Tangdu Hosp, Dept Thorac Surg, Xian, Peoples R China
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Lu, Guofang,Du, Rui,Feng, Bin,et al. A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC[J]. JOURNAL OF INFLAMMATION RESEARCH,2022,15:6729-6743.
APA Lu, Guofang.,Du, Rui.,Feng, Bin.,Wang, Jianlin.,Zhang, Fengrui.,...&Shang, Yulong.(2022).A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC.JOURNAL OF INFLAMMATION RESEARCH,15,6729-6743.
MLA Lu, Guofang,et al."A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC".JOURNAL OF INFLAMMATION RESEARCH 15(2022):6729-6743.
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