Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC
Hepatocellular carcinoma (HCC) is a common malignancy with higher mortality, and means are urgently needed to improve the prognosis. T cell exclusion (TCE) plays a pivotal role in immune evasion, and lncRNAs represent a large group of tumor development and progression modulators. Using the TCGA HCC...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.880288/full |
| _version_ | 1811288867000549376 |
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| author | Xiawei Li Xiawei Li Zhiqian Zhang Mingcheng Liu Xing Fu Jun A Guoan Chen Shian Wu Jin-Tang Dong |
| author_facet | Xiawei Li Xiawei Li Zhiqian Zhang Mingcheng Liu Xing Fu Jun A Guoan Chen Shian Wu Jin-Tang Dong |
| author_sort | Xiawei Li |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a common malignancy with higher mortality, and means are urgently needed to improve the prognosis. T cell exclusion (TCE) plays a pivotal role in immune evasion, and lncRNAs represent a large group of tumor development and progression modulators. Using the TCGA HCC dataset (n=374), we identified 2752 differentially expressed and 702 TCE-associated lncRNAs, of which 336 were in both groups. As identified using the univariate Cox regression analysis, those associated with overall survival (OS) were subjected to the LASSO-COX regression analysis to develop a prognosis signature. The model, which consisted of 11 lncRNAs and was named 11LNCPS for 11-lncRNA prognosis signature, was validated and performed better than two previous models. In addition to OS and TCE, higher 11LNCPS scores had a significant correlation with reduced infiltrations of CD8+ T cells and dendritic cells (DCs) and decreased infiltrations of Th1, Th2, and pro B cells. As expected, these infiltration alterations were significantly associated with worse OS in HCC. Analysis of published data indicates that HCCs with higher 11LNCPS scores were transcriptomically similar to those that responded better to PDL1 inhibitor. Of the 11LNCPS lncRNAs, LINC01134 and AC116025.2 seem more crucial, as their upregulations affected more immune cell types’ infiltrations and were significantly associated with TCE, worse OS, and compromised immune responses in HCC. LncRNAs in the 11LNCPS impacted many cancer-associated biological processes and signaling pathways, particularly those involved in immune function and metabolism. The 11LNCPS should be useful for predicting prognosis and immune responses in HCC. |
| first_indexed | 2024-04-13T03:44:52Z |
| format | Article |
| id | doaj.art-a635cc66d1b44657b730eda9b528966b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T03:44:52Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a635cc66d1b44657b730eda9b528966b2022-12-22T03:04:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.880288880288Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCCXiawei Li0Xiawei Li1Zhiqian Zhang2Mingcheng Liu3Xing Fu4Jun A5Guoan Chen6Shian Wu7Jin-Tang Dong8Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, ChinaLaboratory Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaLaboratory Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaLaboratory Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaLaboratory Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaLaboratory Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaLaboratory Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaDepartment of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, ChinaLaboratory Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaHepatocellular carcinoma (HCC) is a common malignancy with higher mortality, and means are urgently needed to improve the prognosis. T cell exclusion (TCE) plays a pivotal role in immune evasion, and lncRNAs represent a large group of tumor development and progression modulators. Using the TCGA HCC dataset (n=374), we identified 2752 differentially expressed and 702 TCE-associated lncRNAs, of which 336 were in both groups. As identified using the univariate Cox regression analysis, those associated with overall survival (OS) were subjected to the LASSO-COX regression analysis to develop a prognosis signature. The model, which consisted of 11 lncRNAs and was named 11LNCPS for 11-lncRNA prognosis signature, was validated and performed better than two previous models. In addition to OS and TCE, higher 11LNCPS scores had a significant correlation with reduced infiltrations of CD8+ T cells and dendritic cells (DCs) and decreased infiltrations of Th1, Th2, and pro B cells. As expected, these infiltration alterations were significantly associated with worse OS in HCC. Analysis of published data indicates that HCCs with higher 11LNCPS scores were transcriptomically similar to those that responded better to PDL1 inhibitor. Of the 11LNCPS lncRNAs, LINC01134 and AC116025.2 seem more crucial, as their upregulations affected more immune cell types’ infiltrations and were significantly associated with TCE, worse OS, and compromised immune responses in HCC. LncRNAs in the 11LNCPS impacted many cancer-associated biological processes and signaling pathways, particularly those involved in immune function and metabolism. The 11LNCPS should be useful for predicting prognosis and immune responses in HCC.https://www.frontiersin.org/articles/10.3389/fimmu.2022.880288/fullhepatocellular carcinoma (HCC)T cell exclusionlncRNAprognosisLINC01134AC116025.2 |
| spellingShingle | Xiawei Li Xiawei Li Zhiqian Zhang Mingcheng Liu Xing Fu Jun A Guoan Chen Shian Wu Jin-Tang Dong Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC Frontiers in Immunology hepatocellular carcinoma (HCC) T cell exclusion lncRNA prognosis LINC01134 AC116025.2 |
| title | Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC |
| title_full | Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC |
| title_fullStr | Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC |
| title_full_unstemmed | Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC |
| title_short | Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC |
| title_sort | establishment of a lncrna based prognostic gene signature associated with altered immune responses in hcc |
| topic | hepatocellular carcinoma (HCC) T cell exclusion lncRNA prognosis LINC01134 AC116025.2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.880288/full |
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