Identification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis
Background: Hepatocellular carcinoma (HCC) is a typical inflammatory-related malignant tumor with complex immune tolerance microenvironment and poor prognosis. In this study, we aimed to construct a novel immune-related gene signature for the prognosis of HCC patients, exploring tumor microenvironme...
Guardado en:
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/75f9bd9727a84f37a441ab9565849eef |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:75f9bd9727a84f37a441ab9565849eef |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:75f9bd9727a84f37a441ab9565849eef2021-12-01T07:22:27ZIdentification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis1664-802110.3389/fgene.2021.717319https://doaj.org/article/75f9bd9727a84f37a441ab9565849eef2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.717319/fullhttps://doaj.org/toc/1664-8021Background: Hepatocellular carcinoma (HCC) is a typical inflammatory-related malignant tumor with complex immune tolerance microenvironment and poor prognosis. In this study, we aimed to construct a novel immune-related gene signature for the prognosis of HCC patients, exploring tumor microenvironment (TME) cell infiltration characterization and potential mechanisms.Methods: A total of 364 HCC samples with follow-up information in the TCGA-LIHC dataset were analyzed for the training of the prognostic signature. The Least Absolute Shrinkage and Selector Operation (LASSO) regression based on the IRGs was conducted to identify the prognostic genes and establish an immune risk signature. The immune cell infiltration in TME was estimated via the CIBERSORT method. Gene Set Variation Analysis (GSVA) was conducted to compare the biological pathways involved in the low-risk and high-risk groups. Furthermore, paraffin sections of HCC tissue microarrays containing 77 patients from Fudan University Shanghai Cancer Center were used for IHC staining. The clinical characteristics of the 77 HCC patients were collected and summarized for survival analysis validation via the Kaplan–Meier (KM) method.Results: Three-gene signature with close immune correlation (Risk score = EPO * 0.02838 + BIRC5 * 0.02477 + SPP1 * 0.0002044) was constructed eventually and proven to be an effective prognostic factor for HCC patients. The patients were divided into a high-risk and a low-risk group according to the optimal cutoff, and the survival analysis revealed that HCC samples with high-risk immuno-score had significantly poorer outcomes than the low-risk group (p < 0.0001). The results of CIBERSORT suggested that the immune cell activation was relatively higher in the low-risk group with better prognosis. Besides, GSVA analysis showed multiple signaling differences between the high- and low-risk group, indicating that the three-gene prognostic model can affect the prognosis of patients by affecting immune-related mechanisms. Tissue microarray (TMA) results further confirmed that the expression of three genes in HCC tissues was closely related to the prognosis of patients, respectively.Conclusion: In this study, we constructed and validated a robust three-gene signature with close immune correlation in HCC, which presented a reliable performance in the prediction of HCC patients’ survival.Changjing HuangChangjing HuangChenyue ZhangChenyue ZhangJie ShengJie ShengDan WangDan WangYingke ZhaoYingke ZhaoLing QianLing QianLin XieLin XieZhiqiang MengZhiqiang MengFrontiers Media S.A.articlehepatocellular carcinomatumor microenvironmentprognosisEPOBIRC5SPP1GeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
hepatocellular carcinoma tumor microenvironment prognosis EPO BIRC5 SPP1 Genetics QH426-470 |
| spellingShingle |
hepatocellular carcinoma tumor microenvironment prognosis EPO BIRC5 SPP1 Genetics QH426-470 Changjing Huang Changjing Huang Chenyue Zhang Chenyue Zhang Jie Sheng Jie Sheng Dan Wang Dan Wang Yingke Zhao Yingke Zhao Ling Qian Ling Qian Lin Xie Lin Xie Zhiqiang Meng Zhiqiang Meng Identification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis |
| description |
Background: Hepatocellular carcinoma (HCC) is a typical inflammatory-related malignant tumor with complex immune tolerance microenvironment and poor prognosis. In this study, we aimed to construct a novel immune-related gene signature for the prognosis of HCC patients, exploring tumor microenvironment (TME) cell infiltration characterization and potential mechanisms.Methods: A total of 364 HCC samples with follow-up information in the TCGA-LIHC dataset were analyzed for the training of the prognostic signature. The Least Absolute Shrinkage and Selector Operation (LASSO) regression based on the IRGs was conducted to identify the prognostic genes and establish an immune risk signature. The immune cell infiltration in TME was estimated via the CIBERSORT method. Gene Set Variation Analysis (GSVA) was conducted to compare the biological pathways involved in the low-risk and high-risk groups. Furthermore, paraffin sections of HCC tissue microarrays containing 77 patients from Fudan University Shanghai Cancer Center were used for IHC staining. The clinical characteristics of the 77 HCC patients were collected and summarized for survival analysis validation via the Kaplan–Meier (KM) method.Results: Three-gene signature with close immune correlation (Risk score = EPO * 0.02838 + BIRC5 * 0.02477 + SPP1 * 0.0002044) was constructed eventually and proven to be an effective prognostic factor for HCC patients. The patients were divided into a high-risk and a low-risk group according to the optimal cutoff, and the survival analysis revealed that HCC samples with high-risk immuno-score had significantly poorer outcomes than the low-risk group (p < 0.0001). The results of CIBERSORT suggested that the immune cell activation was relatively higher in the low-risk group with better prognosis. Besides, GSVA analysis showed multiple signaling differences between the high- and low-risk group, indicating that the three-gene prognostic model can affect the prognosis of patients by affecting immune-related mechanisms. Tissue microarray (TMA) results further confirmed that the expression of three genes in HCC tissues was closely related to the prognosis of patients, respectively.Conclusion: In this study, we constructed and validated a robust three-gene signature with close immune correlation in HCC, which presented a reliable performance in the prediction of HCC patients’ survival. |
| format |
article |
| author |
Changjing Huang Changjing Huang Chenyue Zhang Chenyue Zhang Jie Sheng Jie Sheng Dan Wang Dan Wang Yingke Zhao Yingke Zhao Ling Qian Ling Qian Lin Xie Lin Xie Zhiqiang Meng Zhiqiang Meng |
| author_facet |
Changjing Huang Changjing Huang Chenyue Zhang Chenyue Zhang Jie Sheng Jie Sheng Dan Wang Dan Wang Yingke Zhao Yingke Zhao Ling Qian Ling Qian Lin Xie Lin Xie Zhiqiang Meng Zhiqiang Meng |
| author_sort |
Changjing Huang |
| title |
Identification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis |
| title_short |
Identification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis |
| title_full |
Identification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis |
| title_fullStr |
Identification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis |
| title_full_unstemmed |
Identification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis |
| title_sort |
identification and validation of a tumor microenvironment-related gene signature in hepatocellular carcinoma prognosis |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/75f9bd9727a84f37a441ab9565849eef |
| work_keys_str_mv |
AT changjinghuang identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT changjinghuang identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT chenyuezhang identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT chenyuezhang identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT jiesheng identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT jiesheng identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT danwang identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT danwang identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT yingkezhao identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT yingkezhao identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT lingqian identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT lingqian identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT linxie identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT linxie identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT zhiqiangmeng identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis AT zhiqiangmeng identificationandvalidationofatumormicroenvironmentrelatedgenesignatureinhepatocellularcarcinomaprognosis |
| _version_ |
1718405419411439616 |