Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma
Tumor mutation burdens (TMBs) act as an indicator of immunotherapeutic responsiveness in various tumors. However, the relationship between TMBs and immune cell infiltrates in hepatocellular carcinoma (HCC) is still obscure. The present study aimed to explore the potential diagnostic markers of TMBs...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/8/1918 |
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| author | Yulan Zhao Ting Huang Pintong Huang |
| author_facet | Yulan Zhao Ting Huang Pintong Huang |
| author_sort | Yulan Zhao |
| collection | DOAJ |
| description | Tumor mutation burdens (TMBs) act as an indicator of immunotherapeutic responsiveness in various tumors. However, the relationship between TMBs and immune cell infiltrates in hepatocellular carcinoma (HCC) is still obscure. The present study aimed to explore the potential diagnostic markers of TMBs for HCC and analyze the role of immune cell infiltration in this pathology. We used OA datasets from The Cancer Genome Atlas database. First, the “maftools” package was used to screen the highest mutation frequency in all samples. R software was used to identify differentially expressed genes (DEGs) according to mutation frequency and perform functional correlation analysis. Then, the gene ontology (GO) enrichment analysis was performed with “clusterProfiler”, “enrichplot”, and “ggplot2” packages. Finally, the correlations between diagnostic markers and infiltrating immune cells were analyzed, and CIBERSORT was used to evaluate the infiltration of immune cells in HCC tissues. As a result, we identified a total of 359 DEGs in this study. These DEGs may affect HCC prognosis by regulating fatty acid metabolism, hypoxia, and the P53 pathway. The top 15 genes were selected as the hub genes through PPI network analysis. <i>SRSF1</i>, <i>SNRPA1</i>, and <i>SRSF3</i> showed strong similarities in biological effects, NCBP2 was demonstrated as a diagnostic marker of HCC, and high NCBP2 expression was significantly correlated with poor over survival (OS) in HCC. In addition, NCBP2 expression was correlated with the infiltration of B cells (r = 0.364, <i>p</i> = 3.30 × 10<sup>−12</sup>), CD8<sup>+</sup> T cells (r = 0.295, <i>p</i> = 2.71 × 10<sup>−8</sup>), CD4<sup>+</sup> T cells, (r = 0.484, <i>p</i> = 1.37 × 10<sup>−21</sup>), macrophages (r = 0.551, <i>p</i> = 1.97 × 10<sup>−28</sup>), neutrophils (r = 0.457, <i>p</i> = 3.26 × 10<sup>−19</sup>), and dendritic cells (r = 0.453, <i>p</i> = 1.97 × 10<sup>−18</sup>). Immune cell infiltration analysis revealed that the degree of central memory T-cell (Tcm) infiltration may be correlated with the HCC process. In conclusion, NCBP2 can be used as diagnostic markers of HCC, and immune cell infiltration plays an important role in the occurrence and progression of HCC. |
| first_indexed | 2024-03-09T13:34:49Z |
| format | Article |
| id | doaj.art-232881fb06054d4a9d83253f3f2ee95a |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T13:34:49Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-232881fb06054d4a9d83253f3f2ee95a2023-11-30T21:13:24ZengMDPI AGDiagnostics2075-44182022-08-01128191810.3390/diagnostics12081918Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular CarcinomaYulan Zhao0Ting Huang1Pintong Huang2Department of Ultrasound in Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Ultrasound in Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Ultrasound in Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaTumor mutation burdens (TMBs) act as an indicator of immunotherapeutic responsiveness in various tumors. However, the relationship between TMBs and immune cell infiltrates in hepatocellular carcinoma (HCC) is still obscure. The present study aimed to explore the potential diagnostic markers of TMBs for HCC and analyze the role of immune cell infiltration in this pathology. We used OA datasets from The Cancer Genome Atlas database. First, the “maftools” package was used to screen the highest mutation frequency in all samples. R software was used to identify differentially expressed genes (DEGs) according to mutation frequency and perform functional correlation analysis. Then, the gene ontology (GO) enrichment analysis was performed with “clusterProfiler”, “enrichplot”, and “ggplot2” packages. Finally, the correlations between diagnostic markers and infiltrating immune cells were analyzed, and CIBERSORT was used to evaluate the infiltration of immune cells in HCC tissues. As a result, we identified a total of 359 DEGs in this study. These DEGs may affect HCC prognosis by regulating fatty acid metabolism, hypoxia, and the P53 pathway. The top 15 genes were selected as the hub genes through PPI network analysis. <i>SRSF1</i>, <i>SNRPA1</i>, and <i>SRSF3</i> showed strong similarities in biological effects, NCBP2 was demonstrated as a diagnostic marker of HCC, and high NCBP2 expression was significantly correlated with poor over survival (OS) in HCC. In addition, NCBP2 expression was correlated with the infiltration of B cells (r = 0.364, <i>p</i> = 3.30 × 10<sup>−12</sup>), CD8<sup>+</sup> T cells (r = 0.295, <i>p</i> = 2.71 × 10<sup>−8</sup>), CD4<sup>+</sup> T cells, (r = 0.484, <i>p</i> = 1.37 × 10<sup>−21</sup>), macrophages (r = 0.551, <i>p</i> = 1.97 × 10<sup>−28</sup>), neutrophils (r = 0.457, <i>p</i> = 3.26 × 10<sup>−19</sup>), and dendritic cells (r = 0.453, <i>p</i> = 1.97 × 10<sup>−18</sup>). Immune cell infiltration analysis revealed that the degree of central memory T-cell (Tcm) infiltration may be correlated with the HCC process. In conclusion, NCBP2 can be used as diagnostic markers of HCC, and immune cell infiltration plays an important role in the occurrence and progression of HCC.https://www.mdpi.com/2075-4418/12/8/1918hepatocellular carcinomatumor mutation burdenimmune cellsThe Cancer Genome AtlasCIBERSORT |
| spellingShingle | Yulan Zhao Ting Huang Pintong Huang Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Diagnostics hepatocellular carcinoma tumor mutation burden immune cells The Cancer Genome Atlas CIBERSORT |
| title | Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma |
| title_full | Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma |
| title_fullStr | Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma |
| title_full_unstemmed | Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma |
| title_short | Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma |
| title_sort | integrated analysis of tumor mutation burden and immune infiltrates in hepatocellular carcinoma |
| topic | hepatocellular carcinoma tumor mutation burden immune cells The Cancer Genome Atlas CIBERSORT |
| url | https://www.mdpi.com/2075-4418/12/8/1918 |
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