Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs
Abstract Background Pyroptosis is closely related to cancer prognosis. In this study, we tried to construct an individualized prognostic risk model for hepatocellular carcinoma (HCC) based on within-sample relative expression orderings (REOs) of pyroptosis-related lncRNAs (PRlncRNAs). Methods RNA-se...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-04-01
|
| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12859-023-05299-9 |
| _version_ | 1827956534955474944 |
|---|---|
| author | Tong Wu Na Li Fengyuan Luo Zhihong Chen Liyuan Ma Tao Hu Guini Hong Hongdong Li |
| author_facet | Tong Wu Na Li Fengyuan Luo Zhihong Chen Liyuan Ma Tao Hu Guini Hong Hongdong Li |
| author_sort | Tong Wu |
| collection | DOAJ |
| description | Abstract Background Pyroptosis is closely related to cancer prognosis. In this study, we tried to construct an individualized prognostic risk model for hepatocellular carcinoma (HCC) based on within-sample relative expression orderings (REOs) of pyroptosis-related lncRNAs (PRlncRNAs). Methods RNA-seq data of 343 HCC samples derived from The Cancer Genome Atlas (TCGA) database were analyzed. PRlncRNAs were detected based on differentially expressed lncRNAs between sample groups clustered by 40 reported pyroptosis-related genes (PRGs). Univariate Cox regression was used to screen out prognosis-related PRlncRNA pairs. Then, based on REOs of prognosis-related PRlncRNA pairs, a risk model for HCC was constructed by combining LASSO and stepwise multivariate Cox regression analysis. Finally, a prognosis-related competing endogenous RNA (ceRNA) network was built based on information about lncRNA–miRNA–mRNA interactions derived from the miRNet and TargetScan databases. Results Hierarchical clustering of HCC patients according to the 40 PRGs identified two groups with a significant survival difference (Kaplan–Meier log-rank, p = 0.026). Between the two groups, 104 differentially expressed lncRNAs were identified (|log2(FC)|> 1 and FDR < 5%). Among them, 83 PRlncRNA pairs showed significant associations between their REOs within HCC samples and overall survival (Univariate Cox regression, p < 0.005). An optimal 11-PRlncRNA-pair prognostic risk model was constructed for HCC. The areas under the curves (AUCs) of time-dependent receiver operating characteristic (ROC) curves of the risk model for 1-, 3-, and 5-year survival were 0.737, 0.705, and 0.797 in the validation set, respectively. Gene Set Enrichment Analysis showed that inflammation-related interleukin signaling pathways were upregulated in the predicted high-risk group (p < 0.05). Tumor immune infiltration analysis revealed a higher abundance of regulatory T cells (Tregs) and M2 macrophages and a lower abundance of CD8 + T cells in the high-risk group, indicating that excessive pyroptosis might occur in high-risk patients. Finally, eleven lncRNA–miRNA–mRNA regulatory axes associated with pyroptosis were established. Conclusion Our risk model allowed us to determine the robustness of the REO-based PRlncRNA prognostic biomarkers in the stratification of HCC patients at high and low risk. The model is also helpful for understanding the molecular mechanisms between pyroptosis and HCC prognosis. High-risk patients may have excessive pyroptosis and thus be less sensitive to immune therapy. |
| first_indexed | 2024-04-09T15:06:35Z |
| format | Article |
| id | doaj.art-9bce5047b06d4c6c8f03fd74d1e07409 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-04-09T15:06:35Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-9bce5047b06d4c6c8f03fd74d1e074092023-04-30T11:30:10ZengBMCBMC Bioinformatics1471-21052023-04-0124111510.1186/s12859-023-05299-9Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairsTong Wu0Na Li1Fengyuan Luo2Zhihong Chen3Liyuan Ma4Tao Hu5Guini Hong6Hongdong Li7School of Medical Information Engineering, Gannan Medical UniversitySchool of Medical Information Engineering, Gannan Medical UniversitySchool of Medical Information Engineering, Gannan Medical UniversitySchool of Medical Information Engineering, Gannan Medical UniversitySchool of Public Health and Health Management, Gannan Medical UniversitySchool of Medical Information Engineering, Gannan Medical UniversitySchool of Medical Information Engineering, Gannan Medical UniversitySchool of Medical Information Engineering, Gannan Medical UniversityAbstract Background Pyroptosis is closely related to cancer prognosis. In this study, we tried to construct an individualized prognostic risk model for hepatocellular carcinoma (HCC) based on within-sample relative expression orderings (REOs) of pyroptosis-related lncRNAs (PRlncRNAs). Methods RNA-seq data of 343 HCC samples derived from The Cancer Genome Atlas (TCGA) database were analyzed. PRlncRNAs were detected based on differentially expressed lncRNAs between sample groups clustered by 40 reported pyroptosis-related genes (PRGs). Univariate Cox regression was used to screen out prognosis-related PRlncRNA pairs. Then, based on REOs of prognosis-related PRlncRNA pairs, a risk model for HCC was constructed by combining LASSO and stepwise multivariate Cox regression analysis. Finally, a prognosis-related competing endogenous RNA (ceRNA) network was built based on information about lncRNA–miRNA–mRNA interactions derived from the miRNet and TargetScan databases. Results Hierarchical clustering of HCC patients according to the 40 PRGs identified two groups with a significant survival difference (Kaplan–Meier log-rank, p = 0.026). Between the two groups, 104 differentially expressed lncRNAs were identified (|log2(FC)|> 1 and FDR < 5%). Among them, 83 PRlncRNA pairs showed significant associations between their REOs within HCC samples and overall survival (Univariate Cox regression, p < 0.005). An optimal 11-PRlncRNA-pair prognostic risk model was constructed for HCC. The areas under the curves (AUCs) of time-dependent receiver operating characteristic (ROC) curves of the risk model for 1-, 3-, and 5-year survival were 0.737, 0.705, and 0.797 in the validation set, respectively. Gene Set Enrichment Analysis showed that inflammation-related interleukin signaling pathways were upregulated in the predicted high-risk group (p < 0.05). Tumor immune infiltration analysis revealed a higher abundance of regulatory T cells (Tregs) and M2 macrophages and a lower abundance of CD8 + T cells in the high-risk group, indicating that excessive pyroptosis might occur in high-risk patients. Finally, eleven lncRNA–miRNA–mRNA regulatory axes associated with pyroptosis were established. Conclusion Our risk model allowed us to determine the robustness of the REO-based PRlncRNA prognostic biomarkers in the stratification of HCC patients at high and low risk. The model is also helpful for understanding the molecular mechanisms between pyroptosis and HCC prognosis. High-risk patients may have excessive pyroptosis and thus be less sensitive to immune therapy.https://doi.org/10.1186/s12859-023-05299-9Hepatocellular carcinomaPyroptosisLong noncoding RNAPrognosisRelative expression ordering |
| spellingShingle | Tong Wu Na Li Fengyuan Luo Zhihong Chen Liyuan Ma Tao Hu Guini Hong Hongdong Li Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs BMC Bioinformatics Hepatocellular carcinoma Pyroptosis Long noncoding RNA Prognosis Relative expression ordering |
| title | Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs |
| title_full | Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs |
| title_fullStr | Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs |
| title_full_unstemmed | Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs |
| title_short | Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs |
| title_sort | screening prognostic markers for hepatocellular carcinoma based on pyroptosis related lncrna pairs |
| topic | Hepatocellular carcinoma Pyroptosis Long noncoding RNA Prognosis Relative expression ordering |
| url | https://doi.org/10.1186/s12859-023-05299-9 |
| work_keys_str_mv | AT tongwu screeningprognosticmarkersforhepatocellularcarcinomabasedonpyroptosisrelatedlncrnapairs AT nali screeningprognosticmarkersforhepatocellularcarcinomabasedonpyroptosisrelatedlncrnapairs AT fengyuanluo screeningprognosticmarkersforhepatocellularcarcinomabasedonpyroptosisrelatedlncrnapairs AT zhihongchen screeningprognosticmarkersforhepatocellularcarcinomabasedonpyroptosisrelatedlncrnapairs AT liyuanma screeningprognosticmarkersforhepatocellularcarcinomabasedonpyroptosisrelatedlncrnapairs AT taohu screeningprognosticmarkersforhepatocellularcarcinomabasedonpyroptosisrelatedlncrnapairs AT guinihong screeningprognosticmarkersforhepatocellularcarcinomabasedonpyroptosisrelatedlncrnapairs AT hongdongli screeningprognosticmarkersforhepatocellularcarcinomabasedonpyroptosisrelatedlncrnapairs |