Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the deadliest malignant tumour worldwide. The metalloproteinase ADAM17 is associated with tumour formation and development; however, its significance in HCC is unclear. This study aimed to investigate the role of ADAM17 in HCC and the correlation between its express...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/23/17069 |
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| author | Tianlong Ding Yang Yu Lei Gao Lin Xiang Bo Xu Baohong Gu Hao Chen |
| author_facet | Tianlong Ding Yang Yu Lei Gao Lin Xiang Bo Xu Baohong Gu Hao Chen |
| author_sort | Tianlong Ding |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is the deadliest malignant tumour worldwide. The metalloproteinase ADAM17 is associated with tumour formation and development; however, its significance in HCC is unclear. This study aimed to investigate the role of ADAM17 in HCC and the correlation between its expression and immune cell infiltration. ADAM17 expression was analysed in pan-cancer and HCC tissues using The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Kaplan–Meier survival analysis displayed a negative association between ADAM17 expression and the overall survival of patients with HCC. High ADAM17 expression was linked to poor tumour/node (T/N) stage and alpha fetoprotein (AFP) levels. Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes analyses revealed the enrichment of several pathways, including epithelial–mesenchymal transition, inflammatory response, Hedgehog, and KRAS signalling, in patients with upregulated ADAM17. ADAM17 was shown to be positively correlated with immune cell infiltration and immune checkpoint expression via the Tumour Immune Estimation Resource (TIMER) database and immunohistochemistry analyses. Protein–protein interaction (PPI) network analysis revealed that ADAM17 plays a core role in cancer development and immune evasion. In vitro and in vivo experiments demonstrated that ADAM17 influences HCC growth and metastasis. In conclusion, ADAM17 is upregulated in most cancers, particularly HCC, and is critical in the development and immune evasion of HCC. |
| first_indexed | 2024-03-09T01:48:55Z |
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| id | doaj.art-68828d12e8854ce7bbb92bfc6c5f66a8 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:48:55Z |
| publishDate | 2023-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-68828d12e8854ce7bbb92bfc6c5f66a82023-12-08T15:18:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124231706910.3390/ijms242317069Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular CarcinomaTianlong Ding0Yang Yu1Lei Gao2Lin Xiang3Bo Xu4Baohong Gu5Hao Chen6The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou 730030, ChinaThe Second Clinical Medical College, Lanzhou University, Lanzhou 730030, ChinaThe Second Clinical Medical College, Lanzhou University, Lanzhou 730030, ChinaThe Second Clinical Medical College, Lanzhou University, Lanzhou 730030, ChinaThe Second Clinical Medical College, Lanzhou University, Lanzhou 730030, ChinaThe Second Clinical Medical College, Lanzhou University, Lanzhou 730030, ChinaThe Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou 730030, ChinaHepatocellular carcinoma (HCC) is the deadliest malignant tumour worldwide. The metalloproteinase ADAM17 is associated with tumour formation and development; however, its significance in HCC is unclear. This study aimed to investigate the role of ADAM17 in HCC and the correlation between its expression and immune cell infiltration. ADAM17 expression was analysed in pan-cancer and HCC tissues using The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Kaplan–Meier survival analysis displayed a negative association between ADAM17 expression and the overall survival of patients with HCC. High ADAM17 expression was linked to poor tumour/node (T/N) stage and alpha fetoprotein (AFP) levels. Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes analyses revealed the enrichment of several pathways, including epithelial–mesenchymal transition, inflammatory response, Hedgehog, and KRAS signalling, in patients with upregulated ADAM17. ADAM17 was shown to be positively correlated with immune cell infiltration and immune checkpoint expression via the Tumour Immune Estimation Resource (TIMER) database and immunohistochemistry analyses. Protein–protein interaction (PPI) network analysis revealed that ADAM17 plays a core role in cancer development and immune evasion. In vitro and in vivo experiments demonstrated that ADAM17 influences HCC growth and metastasis. In conclusion, ADAM17 is upregulated in most cancers, particularly HCC, and is critical in the development and immune evasion of HCC.https://www.mdpi.com/1422-0067/24/23/17069ADAM17hepatocellular carcinomaimmune cell infiltrationprognosisproliferationmetastasis |
| spellingShingle | Tianlong Ding Yang Yu Lei Gao Lin Xiang Bo Xu Baohong Gu Hao Chen Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma International Journal of Molecular Sciences ADAM17 hepatocellular carcinoma immune cell infiltration prognosis proliferation metastasis |
| title | Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma |
| title_full | Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma |
| title_fullStr | Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma |
| title_full_unstemmed | Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma |
| title_short | Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma |
| title_sort | predictive roles of adam17 in patient survival and immune cell infiltration in hepatocellular carcinoma |
| topic | ADAM17 hepatocellular carcinoma immune cell infiltration prognosis proliferation metastasis |
| url | https://www.mdpi.com/1422-0067/24/23/17069 |
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