A Novel Lymphangiogenesis-Related Gene Signature can Predict Prognosis and Immunosuppressive Microenvironment in Patients with Clear Cell Renal Cell Carcinoma
© The author(s)..
Background: Lymphangiogenesis represents a key event in the progression and metastasis of patients with clear cell renal cell carcinoma (ccRCC). Nevertheless, the prognostic value of lymphangiogenesis-related genes (LRGs) in ccRCC patients remains unknown. Method: Differential analyses were performed to identify differentially expressed LRGs between normal and tumor tissues. A univariate Cox analysis was performed to identify differently expressed LRGs associated with overall survival (OS). LASSO and multivariate Cox analyses were performed to construct and optimize the LRG signature. To further explore the molecular characterization of the LRG signature, a functional enrichment analysis, immune signature, somatic mutations, and drug sensitivity were assessed. Immunohistochemistry (IHC) and immunofluorescence staining were performed to validate the relationship between lymphangiogenesis and immunity using our ccRCC samples. Results: Four candidate genes (IL4, CSF2, PROX1, and TEK) were eventually available to construct the LRG signature in the training set. Patients in the high-risk group had a shorter survival than those in the low-risk group. The LRG signature was an independent prognostic factor of OS. These results were confirmed in the validation group. The LRG signature was correlated with immunosuppressive cell infiltration, T cell exhaustion markers, somatic mutations, and drug sensitivity. The IHC and immunofluorescence staining results confirmed the correlation between lymphangiogenesis and CD163+ macrophages, exhausted CD8+PD-1+, and CD8+ LAG3+ T cells. Conclusion: A novel prognostic signature based on LRGs could provide insight into the prognostic evaluation and treatment of ccRCC patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
International journal of medical sciences - 20(2023), 6 vom: 15., Seite 754-770 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Ke [VerfasserIn] |
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| Links: |
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| Themen: |
CD3 Complex |
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| Anmerkungen: |
Date Completed 24.05.2023 Date Revised 24.05.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.7150/ijms.81078 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357161424 |
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| 100 | 1 | |a Chen, Ke |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Novel Lymphangiogenesis-Related Gene Signature can Predict Prognosis and Immunosuppressive Microenvironment in Patients with Clear Cell Renal Cell Carcinoma |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 24.05.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The author(s). | ||
| 520 | |a Background: Lymphangiogenesis represents a key event in the progression and metastasis of patients with clear cell renal cell carcinoma (ccRCC). Nevertheless, the prognostic value of lymphangiogenesis-related genes (LRGs) in ccRCC patients remains unknown. Method: Differential analyses were performed to identify differentially expressed LRGs between normal and tumor tissues. A univariate Cox analysis was performed to identify differently expressed LRGs associated with overall survival (OS). LASSO and multivariate Cox analyses were performed to construct and optimize the LRG signature. To further explore the molecular characterization of the LRG signature, a functional enrichment analysis, immune signature, somatic mutations, and drug sensitivity were assessed. Immunohistochemistry (IHC) and immunofluorescence staining were performed to validate the relationship between lymphangiogenesis and immunity using our ccRCC samples. Results: Four candidate genes (IL4, CSF2, PROX1, and TEK) were eventually available to construct the LRG signature in the training set. Patients in the high-risk group had a shorter survival than those in the low-risk group. The LRG signature was an independent prognostic factor of OS. These results were confirmed in the validation group. The LRG signature was correlated with immunosuppressive cell infiltration, T cell exhaustion markers, somatic mutations, and drug sensitivity. The IHC and immunofluorescence staining results confirmed the correlation between lymphangiogenesis and CD163+ macrophages, exhausted CD8+PD-1+, and CD8+ LAG3+ T cells. Conclusion: A novel prognostic signature based on LRGs could provide insight into the prognostic evaluation and treatment of ccRCC patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a T cell exhaustion. | |
| 650 | 4 | |a clear cell renal cell carcinoma | |
| 650 | 4 | |a lymphangiogenesis | |
| 650 | 4 | |a lymphangiogenesis-related genes | |
| 650 | 4 | |a prognosis | |
| 650 | 4 | |a tumor immune | |
| 650 | 7 | |a CD3 Complex |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 700 | 1 | |a Gao, Mingchao |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yuxia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Wenlong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Junyu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiaodong |e verfasserin |4 aut | |
| 700 | 1 | |a He, Wang |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Tianxin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jian |e verfasserin |4 aut | |
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