Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma
Abstract Background Necroptosis has been reported to play a critical role in occurrence and progression of cancer. The dysregulation of long non-coding RNAs (lncRNAs) is associated with the progression and metastasis of clear cell renal cell carcinoma (CCRCC). However, research on necroptosis-relate...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-023-01194-4 |
| _version_ | 1797779010676064256 |
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| author | Hang Lin Lingzhi Qu Guanqiu Chen Chunfang Zhang Liqing Lu Yongheng Chen |
| author_facet | Hang Lin Lingzhi Qu Guanqiu Chen Chunfang Zhang Liqing Lu Yongheng Chen |
| author_sort | Hang Lin |
| collection | DOAJ |
| description | Abstract Background Necroptosis has been reported to play a critical role in occurrence and progression of cancer. The dysregulation of long non-coding RNAs (lncRNAs) is associated with the progression and metastasis of clear cell renal cell carcinoma (CCRCC). However, research on necroptosis-related lncRNAs in the tumor heterogeneity and prognosis of CCRCC is not completely unclear. This study aimed to analysis the tumor heterogeneity among CCRCC subgroups and construct a CCRCC prognostic signature based on necroptosis-related lncRNAs. Methods Weighted gene co-expression network analysis (WGCNA) was performed to identify necroptosis-related lncRNAs. A preliminary classification of molecular subgroups was performed by non-negative matrix factorization (NMF) consensus clustering analysis. Comprehensive analyses, including fraction genome altered (FGA), tumor mutational burden (TMB), DNA methylation alterations, copy number variations (CNVs), and single nucleotide polymorphisms (SNPs), were performed to explore the potential factors for tumor heterogeneity among the three subgroups. Subsequently, we constructed a predictive signature by multivariate Cox regression. Nomogram, calibration curves, decision curve analysis (DCA), and time-dependent receiver-operating characteristics (ROC) were used to validate and evaluate the signature. Finally, immune correlation analyses, including immune-related signaling pathways, immune cell infiltration status and immune checkpoint gene expression level, were also performed. Results Seven necroptosis-related lncRNAs were screened out by WGCNA, and three subgroups were classified by NMF consensus clustering analysis. There were significant differences in survival prognosis, clinicopathological characteristics, enrichments of immune-related signaling pathway, degree of immune cell infiltration, and expression of immune checkpoint genes in the various subgroups. Most importantly, we found that 26 differentially expressed genes (DEGs) among the 3 subgroups were not affected by DNA methylation alterations, CNVs and SNPs. On the contrary, these DEGs were associated with the seven necroptosis-related lncRNAs. Subsequently, the identified RP11-133F8.2 and RP11-283G6.4 by multivariate Cox regression analysis were involved in the risk model, which could serve as an independent prognostic factor for CCRCC. Finally, qRT-PCR confirmed the differential expression of the two lncRNAs. Conclusions These findings contributed to understanding the function of necroptosis-related lncRNAs in CCRCC and provided new insights of prognostic evaluation and optimal therapeutic strategy for CCRCC. |
| first_indexed | 2024-03-12T23:25:36Z |
| format | Article |
| id | doaj.art-d75e33f03c0b4cac9bc152686d00e988 |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-12T23:25:36Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-d75e33f03c0b4cac9bc152686d00e9882023-07-16T11:13:00ZengBMCEuropean Journal of Medical Research2047-783X2023-07-0128111510.1186/s40001-023-01194-4Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinomaHang Lin0Lingzhi Qu1Guanqiu Chen2Chunfang Zhang3Liqing Lu4Yongheng Chen5Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South UniversityDepartment of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South UniversityDepartment of Urology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Thoracic Surgery, Xiangya Hospital, Central South UniversityDepartment of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South UniversityDepartment of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South UniversityAbstract Background Necroptosis has been reported to play a critical role in occurrence and progression of cancer. The dysregulation of long non-coding RNAs (lncRNAs) is associated with the progression and metastasis of clear cell renal cell carcinoma (CCRCC). However, research on necroptosis-related lncRNAs in the tumor heterogeneity and prognosis of CCRCC is not completely unclear. This study aimed to analysis the tumor heterogeneity among CCRCC subgroups and construct a CCRCC prognostic signature based on necroptosis-related lncRNAs. Methods Weighted gene co-expression network analysis (WGCNA) was performed to identify necroptosis-related lncRNAs. A preliminary classification of molecular subgroups was performed by non-negative matrix factorization (NMF) consensus clustering analysis. Comprehensive analyses, including fraction genome altered (FGA), tumor mutational burden (TMB), DNA methylation alterations, copy number variations (CNVs), and single nucleotide polymorphisms (SNPs), were performed to explore the potential factors for tumor heterogeneity among the three subgroups. Subsequently, we constructed a predictive signature by multivariate Cox regression. Nomogram, calibration curves, decision curve analysis (DCA), and time-dependent receiver-operating characteristics (ROC) were used to validate and evaluate the signature. Finally, immune correlation analyses, including immune-related signaling pathways, immune cell infiltration status and immune checkpoint gene expression level, were also performed. Results Seven necroptosis-related lncRNAs were screened out by WGCNA, and three subgroups were classified by NMF consensus clustering analysis. There were significant differences in survival prognosis, clinicopathological characteristics, enrichments of immune-related signaling pathway, degree of immune cell infiltration, and expression of immune checkpoint genes in the various subgroups. Most importantly, we found that 26 differentially expressed genes (DEGs) among the 3 subgroups were not affected by DNA methylation alterations, CNVs and SNPs. On the contrary, these DEGs were associated with the seven necroptosis-related lncRNAs. Subsequently, the identified RP11-133F8.2 and RP11-283G6.4 by multivariate Cox regression analysis were involved in the risk model, which could serve as an independent prognostic factor for CCRCC. Finally, qRT-PCR confirmed the differential expression of the two lncRNAs. Conclusions These findings contributed to understanding the function of necroptosis-related lncRNAs in CCRCC and provided new insights of prognostic evaluation and optimal therapeutic strategy for CCRCC.https://doi.org/10.1186/s40001-023-01194-4Necroptosis-related lncRNAClear cell renal cell carcinomaTumor heterogeneityPrognosis |
| spellingShingle | Hang Lin Lingzhi Qu Guanqiu Chen Chunfang Zhang Liqing Lu Yongheng Chen Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma European Journal of Medical Research Necroptosis-related lncRNA Clear cell renal cell carcinoma Tumor heterogeneity Prognosis |
| title | Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma |
| title_full | Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma |
| title_fullStr | Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma |
| title_full_unstemmed | Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma |
| title_short | Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma |
| title_sort | comprehensive analysis of necroptosis related lncrna signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma |
| topic | Necroptosis-related lncRNA Clear cell renal cell carcinoma Tumor heterogeneity Prognosis |
| url | https://doi.org/10.1186/s40001-023-01194-4 |
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