Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation
Abstract Background Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-023-02888-9 |
| _version_ | 1797859842272002048 |
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| author | Xia-Hui Lin Dong-ping Li Zhi-Yong Liu Si Zhang Wen-qing Tang Rong-xin Chen Shu-qiang Weng Yu-jen Tseng Ru-yi Xue Ling Dong |
| author_facet | Xia-Hui Lin Dong-ping Li Zhi-Yong Liu Si Zhang Wen-qing Tang Rong-xin Chen Shu-qiang Weng Yu-jen Tseng Ru-yi Xue Ling Dong |
| author_sort | Xia-Hui Lin |
| collection | DOAJ |
| description | Abstract Background Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. Methods Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. Results We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. Conclusions Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression. |
| first_indexed | 2024-04-09T21:36:10Z |
| format | Article |
| id | doaj.art-b884d597764c49a8967e933a458f38bb |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-09T21:36:10Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-b884d597764c49a8967e933a458f38bb2023-03-26T11:18:12ZengBMCCancer Cell International1475-28672023-03-0123112010.1186/s12935-023-02888-9Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validationXia-Hui Lin0Dong-ping Li1Zhi-Yong Liu2Si Zhang3Wen-qing Tang4Rong-xin Chen5Shu-qiang Weng6Yu-jen Tseng7Ru-yi Xue8Ling Dong9Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan UniversityDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan UniversityDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan UniversityKey Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan UniversityDepartment of Digestive Diseases, Huashan Hospital, Fudan UniversityDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan UniversityDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan UniversityAbstract Background Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. Methods Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. Results We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. Conclusions Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression.https://doi.org/10.1186/s12935-023-02888-9Hepatocellular carcinomaPrognosisImmune gene signatureCompeting endogenous RNA |
| spellingShingle | Xia-Hui Lin Dong-ping Li Zhi-Yong Liu Si Zhang Wen-qing Tang Rong-xin Chen Shu-qiang Weng Yu-jen Tseng Ru-yi Xue Ling Dong Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation Cancer Cell International Hepatocellular carcinoma Prognosis Immune gene signature Competing endogenous RNA |
| title | Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation |
| title_full | Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation |
| title_fullStr | Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation |
| title_full_unstemmed | Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation |
| title_short | Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation |
| title_sort | six immune related promising biomarkers may promote hepatocellular carcinoma prognosis a bioinformatics analysis and experimental validation |
| topic | Hepatocellular carcinoma Prognosis Immune gene signature Competing endogenous RNA |
| url | https://doi.org/10.1186/s12935-023-02888-9 |
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