机构：[1]Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming, China,外科科室器官移植中心昆明医科大学附属第一医院[2]Department of Otorhinolaryngology, The First Affiliated Hospital of Kunming Medical University, Kunming, China,外科科室耳鼻咽喉科昆明医科大学附属第一医院[3]Gastrointestinal and Hernia Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, China,外科科室普通外科普通外一科(胃肠与疝外科)昆明医科大学附属第一医院[4]Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China,[5]Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,[6]School of Automation Science and Engineering, South China University of Technology, Guangzhou, China
Background The mechanistic basis for relapsed hepatocellular carcinoma (HCC) remains poorly understood. Recent research has highlighted the important roles of long non-coding RNAs (lncRNAs) in HCC. However, there are only a few studies on the association between lncRNAs and HCC relapse.</p> Methods Differentially expressed lncRNAs and mRNAs between a primary HCC group and relapsed HCC group were identified using the edge R package to analyze the GSE101432 dataset. The differentially expressed lncRNAs and mRNAs were used to construct a lncRNA-mRNA co-expression network. Weighted gene co-expression network analysis followed by Gene Ontology (GO) enrichment analyses were conducted on the database. Furthermore, correlation and survival analyses were performed using The Cancer Genome Atlas database, and expression in the clinical samples was verified by qRT-PCR. Thereafter, we inputted the genes from the two groups into the HCC TNM stage and tumor grade database from TCGA. Finally, we performed Kaplan-Meier survival analysis on the lncRNAs related to relapsed HCC.</p> Results In this study, lncRNAs and mRNAs associated with HCC relapse were identified. Two gene modules were found to be closely linked to this. The GO terms in the yellow and black modules were related to cell proliferation, differentiation, and survival, as well as some transcription-related biological processes. Through qRT-PCR, we found that the expression levels of LINC00941 and LINC00668 in relapsed HCC were higher than those in primary HCC. Further, mRNA levels of LOX, OTX1, MICB, NDUFA4L2, BAIAP2L2, and KCTD17 were changed in relapsed HCC compared to levels in primary HCC. In addition, we verified that these genes could predict the overall survival and recurrence-free survival of HCC. Moreover, we found that LINC00668 and LINC00941 could affect tumor grade and TNM stages. In total, we identified and validated two lncRNAs (LINC00941 and LINC00668) and six mRNAs (LOX, MICB, OTX1, BAIAP2L2, KCTD17, NDUFA4L2) associated with HCC relapse.</p> Conclusion In summary, we identified the key gene modules and central genes associated with relapsed HCC and constructed lncRNA-mRNA networks related to this. These genes are likely to have potential prognostic value for relapsed HCC and might shed new light on novel biomarkers or diagnostic targets for relapsed HCC.</p>
基金：
National Natural Science Foundation of China (No. 81960123
and 81760119).
第一作者机构：[1]Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming, China,
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Yuan Fang,Yang Yang,XiaoLi Zhang,et al.A Co-Expression Network Reveals the Potential Regulatory Mechanism of lncRNAs in Relapsed Hepatocellular Carcinoma[J].FRONTIERS IN ONCOLOGY.2021,11:doi:10.3389/fonc.2021.745166.
APA：
Yuan Fang,Yang Yang,XiaoLi Zhang,Na Li,Bo Yuan...&HanFei Huang.(2021).A Co-Expression Network Reveals the Potential Regulatory Mechanism of lncRNAs in Relapsed Hepatocellular Carcinoma.FRONTIERS IN ONCOLOGY,11,
MLA：
Yuan Fang,et al."A Co-Expression Network Reveals the Potential Regulatory Mechanism of lncRNAs in Relapsed Hepatocellular Carcinoma".FRONTIERS IN ONCOLOGY 11.(2021)
