The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma
Colon adenocarcinoma (COAD) is one of the most common clinically malignant tumours of the digestive system, with high incidence and mortality and poor prognosis. Interferon-gamma (IFN-γ) and long noncoding RNAs (lncRNAs) have prognostic values and were closely associated with immune microenvironment...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.876660/full |
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| author | Cong Liu Cong Liu Cong Liu Dingwei Liu Dingwei Liu Dingwei Liu Fangfei Wang Fangfei Wang Fangfei Wang Jun Xie Jun Xie Jun Xie Yang Liu Yang Liu Yang Liu Huan Wang Huan Wang Huan Wang Jianfang Rong Jianfang Rong Jianfang Rong Jinliang Xie Jinliang Xie Jinliang Xie Jinyun Wang Jinyun Wang Jinyun Wang Rong Zeng Rong Zeng Rong Zeng Yong Xie Yong Xie Yong Xie |
| author_facet | Cong Liu Cong Liu Cong Liu Dingwei Liu Dingwei Liu Dingwei Liu Fangfei Wang Fangfei Wang Fangfei Wang Jun Xie Jun Xie Jun Xie Yang Liu Yang Liu Yang Liu Huan Wang Huan Wang Huan Wang Jianfang Rong Jianfang Rong Jianfang Rong Jinliang Xie Jinliang Xie Jinliang Xie Jinyun Wang Jinyun Wang Jinyun Wang Rong Zeng Rong Zeng Rong Zeng Yong Xie Yong Xie Yong Xie |
| author_sort | Cong Liu |
| collection | DOAJ |
| description | Colon adenocarcinoma (COAD) is one of the most common clinically malignant tumours of the digestive system, with high incidence and mortality and poor prognosis. Interferon-gamma (IFN-γ) and long noncoding RNAs (lncRNAs) have prognostic values and were closely associated with immune microenvironment in COAD. Thus, identifying IFN-γ-related lncRNAs may be valuable in predicting the survival of patients with COAD. In this study, we identified IFN-γ-related lncRNAs and divided COAD patients from the Cancer Genome Atlas (TCGA) database into training and validation sets. Pearson’s correlation analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were performed to select IFN-γ-related lncRNA-associated prognoses. Thirteen lncRNAs (AC025165.8, AC091633.3, FENDRR, LINC00882, LINC01828, LINC01829, MYOSLID, RP11-154H23.4, RP11-20J15.3, RP11-324L17.1, RP11-342A23.2, RP11-805I24.3, SERTAD4-AS1) were identified to construct an IFN-γ-related lncRNA prognostic signature in TCGA training (n =213) and validation (n =213) cohorts. COAD patient risk scores were calculated and classified into high- and low-risk groups based on the median value of the risk scores in each dataset. We compared the overall survival (OS) of patients stratified by age, gender, and stage. The OS in the high-risk group was significantly shorter than that in the low-risk group. In addition, the clinical nomogram incorporating the prognostic signature and clinical features showed a high concordance index of 0.78 and accurately predicted 1-, 3-, and 5-year survival times among COAD patients in the high- and low-risk groups. Based on the risk model, the high- and low-risk groups exhibited distinct differences in the immune system by gene set enrichment analysis (GSEA) functional annotation, and differentially expressed genes (DEGs) between the high- and low-risk groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We investigated the expression of multiple immune checkpoint genes in the high- and low-risk groups and plotted Kaplan-Meier survival curves, indicating that immune checkpoint genes, such as LAG3 and PD. L1, STING and TIM 3, were also expressed differently between the two risk groups. Subsequently, there were dramatic differences in mutated genes, SNV (single nucleotide variants) classes, variant types and variant allele frequencies between low- and high-risk patients with COAD. Patients stratified by risk scores had different sensitivities to common chemotherapeutic agents. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) assays to demonstrate that three lncRNAs were significantly differentially expressed in COAD tissues and adjacent normal tissues. Considered together, a thirteen-lncRNA prognostic signature has great potential to be a prognostic biomarker and could play an essential role in the immune microenvironment of COAD. |
| first_indexed | 2024-12-12T08:31:41Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T08:31:41Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-95e03b1e0d2a4a74b7ace7e7c4d50a7f2022-12-22T00:31:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.876660876660The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon AdenocarcinomaCong Liu0Cong Liu1Cong Liu2Dingwei Liu3Dingwei Liu4Dingwei Liu5Fangfei Wang6Fangfei Wang7Fangfei Wang8Jun Xie9Jun Xie10Jun Xie11Yang Liu12Yang Liu13Yang Liu14Huan Wang15Huan Wang16Huan Wang17Jianfang Rong18Jianfang Rong19Jianfang Rong20Jinliang Xie21Jinliang Xie22Jinliang Xie23Jinyun Wang24Jinyun Wang25Jinyun Wang26Rong Zeng27Rong Zeng28Rong Zeng29Yong Xie30Yong Xie31Yong Xie32Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaGastroenterology Institute of Jiangxi Province, Nanchang, ChinaKey Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, ChinaColon adenocarcinoma (COAD) is one of the most common clinically malignant tumours of the digestive system, with high incidence and mortality and poor prognosis. Interferon-gamma (IFN-γ) and long noncoding RNAs (lncRNAs) have prognostic values and were closely associated with immune microenvironment in COAD. Thus, identifying IFN-γ-related lncRNAs may be valuable in predicting the survival of patients with COAD. In this study, we identified IFN-γ-related lncRNAs and divided COAD patients from the Cancer Genome Atlas (TCGA) database into training and validation sets. Pearson’s correlation analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were performed to select IFN-γ-related lncRNA-associated prognoses. Thirteen lncRNAs (AC025165.8, AC091633.3, FENDRR, LINC00882, LINC01828, LINC01829, MYOSLID, RP11-154H23.4, RP11-20J15.3, RP11-324L17.1, RP11-342A23.2, RP11-805I24.3, SERTAD4-AS1) were identified to construct an IFN-γ-related lncRNA prognostic signature in TCGA training (n =213) and validation (n =213) cohorts. COAD patient risk scores were calculated and classified into high- and low-risk groups based on the median value of the risk scores in each dataset. We compared the overall survival (OS) of patients stratified by age, gender, and stage. The OS in the high-risk group was significantly shorter than that in the low-risk group. In addition, the clinical nomogram incorporating the prognostic signature and clinical features showed a high concordance index of 0.78 and accurately predicted 1-, 3-, and 5-year survival times among COAD patients in the high- and low-risk groups. Based on the risk model, the high- and low-risk groups exhibited distinct differences in the immune system by gene set enrichment analysis (GSEA) functional annotation, and differentially expressed genes (DEGs) between the high- and low-risk groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We investigated the expression of multiple immune checkpoint genes in the high- and low-risk groups and plotted Kaplan-Meier survival curves, indicating that immune checkpoint genes, such as LAG3 and PD. L1, STING and TIM 3, were also expressed differently between the two risk groups. Subsequently, there were dramatic differences in mutated genes, SNV (single nucleotide variants) classes, variant types and variant allele frequencies between low- and high-risk patients with COAD. Patients stratified by risk scores had different sensitivities to common chemotherapeutic agents. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) assays to demonstrate that three lncRNAs were significantly differentially expressed in COAD tissues and adjacent normal tissues. Considered together, a thirteen-lncRNA prognostic signature has great potential to be a prognostic biomarker and could play an essential role in the immune microenvironment of COAD.https://www.frontiersin.org/articles/10.3389/fonc.2022.876660/fullcolon adenocarcinomalncRNAIFN-γtumour immune microenvironmentprognosis |
| spellingShingle | Cong Liu Cong Liu Cong Liu Dingwei Liu Dingwei Liu Dingwei Liu Fangfei Wang Fangfei Wang Fangfei Wang Jun Xie Jun Xie Jun Xie Yang Liu Yang Liu Yang Liu Huan Wang Huan Wang Huan Wang Jianfang Rong Jianfang Rong Jianfang Rong Jinliang Xie Jinliang Xie Jinliang Xie Jinyun Wang Jinyun Wang Jinyun Wang Rong Zeng Rong Zeng Rong Zeng Yong Xie Yong Xie Yong Xie The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma Frontiers in Oncology colon adenocarcinoma lncRNA IFN-γ tumour immune microenvironment prognosis |
| title | The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma |
| title_full | The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma |
| title_fullStr | The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma |
| title_full_unstemmed | The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma |
| title_short | The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma |
| title_sort | interferon gamma related long noncoding rna signature predicts prognosis and indicates immune microenvironment infiltration in colon adenocarcinoma |
| topic | colon adenocarcinoma lncRNA IFN-γ tumour immune microenvironment prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.876660/full |
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