Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm
Abstract Emerging evidence has highlighted that the immune and stromal cells formed the majority of tumor microenvironment (TME) which are served as important roles in tumor progression. In our study, we aimed to screen vital prognostic signature associated with TME in clear cell renal cell carcinom...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-06-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2983 |
| _version_ | 1811319887096709120 |
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| author | Jun Luo Yi Xie Yuxiao Zheng Chenji Wang Feng Qi Jiateng Hu Yaoting Xu |
| author_facet | Jun Luo Yi Xie Yuxiao Zheng Chenji Wang Feng Qi Jiateng Hu Yaoting Xu |
| author_sort | Jun Luo |
| collection | DOAJ |
| description | Abstract Emerging evidence has highlighted that the immune and stromal cells formed the majority of tumor microenvironment (TME) which are served as important roles in tumor progression. In our study, we aimed to screen vital prognostic signature associated with TME in clear cell renal cell carcinoma (ccRCC). We obtained total 611 samples from TCGA database consisting of transcriptome profiles and clinical data. ESTIMATE algorithm was applied to estimate the infiltrating fractions of immune/stromal cells. We found that the immune scores revealed more prognostic significance in overall survival and positive associations with risk clinical factors than stromal scores. We carried out differential expression analysis between Immunescore and stromalscore groups to obtain the 72 intersect genes. Protein to protein interaction (PPI) network and functional analysis was performed to indicate potential altered pathways. Additionally, we further conducted multivariate Cox analysis to identify 12 hub genes associated highly with TME of ccRCC using a stepwise regression procedure. Accordingly, risk score was constructed from the multivariate Cox results and Receiver Operating Characteristic (ROC) curve was used to assess the predictive value (AUC = 0.781). The ccRCC patients with high risk scores suffered poor survival outcomes than that with low risk scores. In the validation cohort from GSE53757, TNFSF13B, CASP5, and GJB6 correlated positively with tumor stages, while FREM1 negatively correlated with tumor stages. Importantly, we further observed that TNFSF13B, CASP5 and XCR1 showed the remarkable correlations with tumor‐infiltrating immune cells. Taken together, our research identified specific signatures that related to the infiltration of stromal and immune cells in TME of ccRCC using the transciptome profiles, which reached a comprehensive understanding of tumor microenvironment in ccRCC. |
| first_indexed | 2024-04-13T12:50:04Z |
| format | Article |
| id | doaj.art-4106c8c8893043f4afcb59298594f05e |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-13T12:50:04Z |
| publishDate | 2020-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-4106c8c8893043f4afcb59298594f05e2022-12-22T02:46:15ZengWileyCancer Medicine2045-76342020-06-019124310432310.1002/cam4.2983Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithmJun Luo0Yi Xie1Yuxiao Zheng2Chenji Wang3Feng Qi4Jiateng Hu5Yaoting Xu6Department of Urology Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine Shanghai ChinaThe First Clinical Medical College of Nanjing Medical University Nanjing ChinaDepartment of Urology Jiangsu Cancer Hospital Jiangsu Institute of Cancer Research Nanjing Medical University Nanjing ChinaState Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences Fudan University Shanghai ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaThe First Clinical Medical College of Nanjing Medical University Nanjing ChinaDepartment of Urology Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine Shanghai ChinaAbstract Emerging evidence has highlighted that the immune and stromal cells formed the majority of tumor microenvironment (TME) which are served as important roles in tumor progression. In our study, we aimed to screen vital prognostic signature associated with TME in clear cell renal cell carcinoma (ccRCC). We obtained total 611 samples from TCGA database consisting of transcriptome profiles and clinical data. ESTIMATE algorithm was applied to estimate the infiltrating fractions of immune/stromal cells. We found that the immune scores revealed more prognostic significance in overall survival and positive associations with risk clinical factors than stromal scores. We carried out differential expression analysis between Immunescore and stromalscore groups to obtain the 72 intersect genes. Protein to protein interaction (PPI) network and functional analysis was performed to indicate potential altered pathways. Additionally, we further conducted multivariate Cox analysis to identify 12 hub genes associated highly with TME of ccRCC using a stepwise regression procedure. Accordingly, risk score was constructed from the multivariate Cox results and Receiver Operating Characteristic (ROC) curve was used to assess the predictive value (AUC = 0.781). The ccRCC patients with high risk scores suffered poor survival outcomes than that with low risk scores. In the validation cohort from GSE53757, TNFSF13B, CASP5, and GJB6 correlated positively with tumor stages, while FREM1 negatively correlated with tumor stages. Importantly, we further observed that TNFSF13B, CASP5 and XCR1 showed the remarkable correlations with tumor‐infiltrating immune cells. Taken together, our research identified specific signatures that related to the infiltration of stromal and immune cells in TME of ccRCC using the transciptome profiles, which reached a comprehensive understanding of tumor microenvironment in ccRCC.https://doi.org/10.1002/cam4.2983biomarkersclear cell renal cell carcinoma (ccRCC)immune infiltratesimmune/stromal scorestumor microenvironment (TME) |
| spellingShingle | Jun Luo Yi Xie Yuxiao Zheng Chenji Wang Feng Qi Jiateng Hu Yaoting Xu Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm Cancer Medicine biomarkers clear cell renal cell carcinoma (ccRCC) immune infiltrates immune/stromal scores tumor microenvironment (TME) |
| title | Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm |
| title_full | Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm |
| title_fullStr | Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm |
| title_full_unstemmed | Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm |
| title_short | Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm |
| title_sort | comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the estimate algorithm |
| topic | biomarkers clear cell renal cell carcinoma (ccRCC) immune infiltrates immune/stromal scores tumor microenvironment (TME) |
| url | https://doi.org/10.1002/cam4.2983 |
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