Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment
BackgroundThe crucial role of DTL has been previously implicated in genomic stability; however, its prognostic value and its relation with tumor immunity in hepatocellular carcinoma (HCC) remain to be further explored.MethodsTranscriptional and mutational datasets as well as clinical information wer...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.834606/full |
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| author | Zuyin Li Zuyin Li Rangrang Wang Rangrang Wang Chen Qiu Can Cao Jianming Zhang Jianming Zhang Jun Ge Yuanping Shi |
| author_facet | Zuyin Li Zuyin Li Rangrang Wang Rangrang Wang Chen Qiu Can Cao Jianming Zhang Jianming Zhang Jun Ge Yuanping Shi |
| author_sort | Zuyin Li |
| collection | DOAJ |
| description | BackgroundThe crucial role of DTL has been previously implicated in genomic stability; however, its prognostic value and its relation with tumor immunity in hepatocellular carcinoma (HCC) remain to be further explored.MethodsTranscriptional and mutational datasets as well as clinical information were retrieved from the GEO, ICGC, and TCGA databases. Differentially expressed genes (DEGs) were obtained from the comparison of DTLhigh and DTLlow expression groups of the TCGA-HCC cohort. Those genes were under KEGG and gene ontology (GO) analyses to decipher the influence of the DTL gene on the biological behavior of HCC tumor cells. The survival status and mutational characteristics of patients according to DTL levels were depicted and analyzed. The DTL overexpression in HCC and its impact on prognosis were further confirmed by a cohort of 114 HCC patients (validation cohort). The TIMER, GEPIA, and TISIDB databases were adopted to investigate the potential relations between DTL levels and the status of immune cells, as well as immune cell infiltrations.ResultsThe DTL gene is overexpressed in tumor tissues compared with distant non-malignant liver tissues, and DTL overexpression in HCC would enhance the HCC cells in the activities of cell cycle and division. HCC patients with high DTL expression have unfavorable clinical outcomes and harbor more somatic mutations than those with low DTL expression, and multivariate analysis also revealed that DTL overexpression could act as an independent biomarker for prognosis. Moreover, the DTL gene was positively linked to marker sets of infiltrating activated CD8+ and CD4+ T cells; however, these cells demonstrated to be functionally exhausted.ConclusionsPatients with a DTL overexpression phenotype in HCC have poorer prognosis than those in the DTLlow group due to the role of the DTL gene in the process of pro-cell proliferation, accompanied by the immunosuppressive microenvironment and T cell exhaustion. |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T17:29:33Z |
| publishDate | 2022-03-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-73da4ee9f4074709990ac4e4ba32be6e2022-12-22T02:37:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.834606834606Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor MicroenvironmentZuyin Li0Zuyin Li1Rangrang Wang2Rangrang Wang3Chen Qiu4Can Cao5Jianming Zhang6Jianming Zhang7Jun Ge8Yuanping Shi9Department of Hepatobiliary Surgery, Peking University Organ Transplantation Institute, Peking University People’s Hospital, Beijing, ChinaDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaCenter of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, School of Medicine, Tongji University, Shanghai, ChinaDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of General Surgery, The 306th Hospital of People's Liberation Army (PLA)-Peking University Teaching Hospital, Beijing, ChinaDepartment of Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackgroundThe crucial role of DTL has been previously implicated in genomic stability; however, its prognostic value and its relation with tumor immunity in hepatocellular carcinoma (HCC) remain to be further explored.MethodsTranscriptional and mutational datasets as well as clinical information were retrieved from the GEO, ICGC, and TCGA databases. Differentially expressed genes (DEGs) were obtained from the comparison of DTLhigh and DTLlow expression groups of the TCGA-HCC cohort. Those genes were under KEGG and gene ontology (GO) analyses to decipher the influence of the DTL gene on the biological behavior of HCC tumor cells. The survival status and mutational characteristics of patients according to DTL levels were depicted and analyzed. The DTL overexpression in HCC and its impact on prognosis were further confirmed by a cohort of 114 HCC patients (validation cohort). The TIMER, GEPIA, and TISIDB databases were adopted to investigate the potential relations between DTL levels and the status of immune cells, as well as immune cell infiltrations.ResultsThe DTL gene is overexpressed in tumor tissues compared with distant non-malignant liver tissues, and DTL overexpression in HCC would enhance the HCC cells in the activities of cell cycle and division. HCC patients with high DTL expression have unfavorable clinical outcomes and harbor more somatic mutations than those with low DTL expression, and multivariate analysis also revealed that DTL overexpression could act as an independent biomarker for prognosis. Moreover, the DTL gene was positively linked to marker sets of infiltrating activated CD8+ and CD4+ T cells; however, these cells demonstrated to be functionally exhausted.ConclusionsPatients with a DTL overexpression phenotype in HCC have poorer prognosis than those in the DTLlow group due to the role of the DTL gene in the process of pro-cell proliferation, accompanied by the immunosuppressive microenvironment and T cell exhaustion.https://www.frontiersin.org/articles/10.3389/fimmu.2022.834606/fullDTLDNA replicationcell cycleimmune cell infiltrationprognosis |
| spellingShingle | Zuyin Li Zuyin Li Rangrang Wang Rangrang Wang Chen Qiu Can Cao Jianming Zhang Jianming Zhang Jun Ge Yuanping Shi Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment Frontiers in Immunology DTL DNA replication cell cycle immune cell infiltration prognosis |
| title | Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment |
| title_full | Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment |
| title_fullStr | Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment |
| title_full_unstemmed | Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment |
| title_short | Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment |
| title_sort | role of dtl in hepatocellular carcinoma and its impact on the tumor microenvironment |
| topic | DTL DNA replication cell cycle immune cell infiltration prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.834606/full |
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