Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinoma
Background: Kidney renal clear cell carcinoma (KIRC) is a common cancer of the adult urological system. Recent developments in tumor immunology and pyroptosis biology have provided new directions for kidney cancer treatment. Therefore, there is an urgent need to identify potential targets and progno...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323000797 |
| _version_ | 1797802874050183168 |
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| author | Minhao Zhang Yi-Fan Liu Yue Gao Chenggui Zhao Ming Chen Ke-Hao Pan |
| author_facet | Minhao Zhang Yi-Fan Liu Yue Gao Chenggui Zhao Ming Chen Ke-Hao Pan |
| author_sort | Minhao Zhang |
| collection | DOAJ |
| description | Background: Kidney renal clear cell carcinoma (KIRC) is a common cancer of the adult urological system. Recent developments in tumor immunology and pyroptosis biology have provided new directions for kidney cancer treatment. Therefore, there is an urgent need to identify potential targets and prognostic biomarkers for the combination of immunotherapy and pyroptosis-targeted therapy. Methods: The expression of immune-pyroptosis-related differentially expressed genes (IPR-DEGs) between KIRC and healthy tissues was examined using the Gene Expression Omnibus datasets. The GSE168845 dataset was selected for subsequent analyses. Data of 1793 human immune-related genes were downloaded from the ImmPort database (https://www.immport.org./home), while those of 33 pyroptosis-related genes were extracted from previous reviews. The independent prognostic value of IPR-DEGs was determined using differential expression, prognostic, and univariate and multivariate Cox regression analyses. The GSE53757 dataset was used to further verify the GSDMB and PYCARD levels. In our cohorts, the association among DEGs and clinicopathological features and overall survival was analyzed. The least absolute shrinkage and selection operator Cox regression model was established to evaluate the correlation of IPR-DEGs with the immune score, immune checkpoint gene expression, and one-class logistic regression (OCLR) score. KIRC cells and clinical tissue samples were subjected to quantitative real-time polymerase chain reaction to examine the GSDMB and PYCARD mRNA levels. The GSDMB and PYCARD levels in a healthy kidney cell line (HK-2 cells) and two KIRC cell lines (786-O and Caki-1 cells) were verified. The tissue levels of GSDMB and PYCARD were evaluated using immunohistochemical analysis. GSDMB and PYCARD were knocked down in 786-O cells using short-interfering RNA. Cell proliferation was examined using the cell counting kit-8 assay. Cell migration was measured by transwell migration assays Results: GSDMB and PYCARD were determined to be IPR-DEGs with independent prognostic values. A risk prognostic model based on GSDMB and PYCARD was successfully established. In the GSE53757 dataset, the GSDMB and PYCARD levels in KIRC tissues were significantly higher than those in healthy tissues. The GSDMB and PYCARD expression was related to T stage and OS in our cohort. The GSDMB and PYCARD levels were significantly correlated with the immune score, immune checkpoint gene expression, and OCLR score. The results of experimental studies were consistent with those of bioinformatics analysis. The GSDMB and PYCARD levels in KIRC cells were significantly upregulated when compared with those in healthy kidney cells. Consistently, GSDMB and PYCARD in KIRC tissues were significantly upregulated when compared with those in adjacent healthy kidney tissues. GSDMB and PYCARD knockdown significantly decreased 786-O cell proliferation (p < 0.05). Transwell migration result reflects that silencing GSDMB and PYCARD inhibited 786-O cell migration (p < 0.05) . Conclusions: GSDMB and PYCARD are potential targets and effective prognostic biomarkers for the combination of immunotherapy and pyroptosis-targeted therapy in KIRC. |
| first_indexed | 2024-03-13T05:12:20Z |
| format | Article |
| id | doaj.art-b84105697ff646328aef369604171703 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-13T05:12:20Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-b84105697ff646328aef3696041717032023-06-16T05:09:16ZengElsevierTranslational Oncology1936-52332023-08-0134101693Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinomaMinhao Zhang0Yi-Fan Liu1Yue Gao2Chenggui Zhao3Ming Chen4Ke-Hao Pan5Department of Urology, XiShan People's Hospital Of Wuxi City, Wuxi, ChinaSoutheast University, 87 Dingjia Bridge Hunan Road, Nanjing, ChinaAffiliated Zhongda Hospital of Southeast University, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, ChinaAffiliated Zhongda Hospital of Southeast University, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, ChinaDepartment of Urology, Affiliated Zhongda Hospital of Southeast University, Lishui District People's Hospital, 87 Dingjia Bridge Hunan Road, Nanjing, ChinaAffiliated Zhongda Hospital of Southeast University, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, China; Corresponding author.Background: Kidney renal clear cell carcinoma (KIRC) is a common cancer of the adult urological system. Recent developments in tumor immunology and pyroptosis biology have provided new directions for kidney cancer treatment. Therefore, there is an urgent need to identify potential targets and prognostic biomarkers for the combination of immunotherapy and pyroptosis-targeted therapy. Methods: The expression of immune-pyroptosis-related differentially expressed genes (IPR-DEGs) between KIRC and healthy tissues was examined using the Gene Expression Omnibus datasets. The GSE168845 dataset was selected for subsequent analyses. Data of 1793 human immune-related genes were downloaded from the ImmPort database (https://www.immport.org./home), while those of 33 pyroptosis-related genes were extracted from previous reviews. The independent prognostic value of IPR-DEGs was determined using differential expression, prognostic, and univariate and multivariate Cox regression analyses. The GSE53757 dataset was used to further verify the GSDMB and PYCARD levels. In our cohorts, the association among DEGs and clinicopathological features and overall survival was analyzed. The least absolute shrinkage and selection operator Cox regression model was established to evaluate the correlation of IPR-DEGs with the immune score, immune checkpoint gene expression, and one-class logistic regression (OCLR) score. KIRC cells and clinical tissue samples were subjected to quantitative real-time polymerase chain reaction to examine the GSDMB and PYCARD mRNA levels. The GSDMB and PYCARD levels in a healthy kidney cell line (HK-2 cells) and two KIRC cell lines (786-O and Caki-1 cells) were verified. The tissue levels of GSDMB and PYCARD were evaluated using immunohistochemical analysis. GSDMB and PYCARD were knocked down in 786-O cells using short-interfering RNA. Cell proliferation was examined using the cell counting kit-8 assay. Cell migration was measured by transwell migration assays Results: GSDMB and PYCARD were determined to be IPR-DEGs with independent prognostic values. A risk prognostic model based on GSDMB and PYCARD was successfully established. In the GSE53757 dataset, the GSDMB and PYCARD levels in KIRC tissues were significantly higher than those in healthy tissues. The GSDMB and PYCARD expression was related to T stage and OS in our cohort. The GSDMB and PYCARD levels were significantly correlated with the immune score, immune checkpoint gene expression, and OCLR score. The results of experimental studies were consistent with those of bioinformatics analysis. The GSDMB and PYCARD levels in KIRC cells were significantly upregulated when compared with those in healthy kidney cells. Consistently, GSDMB and PYCARD in KIRC tissues were significantly upregulated when compared with those in adjacent healthy kidney tissues. GSDMB and PYCARD knockdown significantly decreased 786-O cell proliferation (p < 0.05). Transwell migration result reflects that silencing GSDMB and PYCARD inhibited 786-O cell migration (p < 0.05) . Conclusions: GSDMB and PYCARD are potential targets and effective prognostic biomarkers for the combination of immunotherapy and pyroptosis-targeted therapy in KIRC.http://www.sciencedirect.com/science/article/pii/S1936523323000797Immune-pyroptosisKidney renal clear cell carcinomaPrognosisBiomarkersPyroptosis |
| spellingShingle | Minhao Zhang Yi-Fan Liu Yue Gao Chenggui Zhao Ming Chen Ke-Hao Pan Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinoma Translational Oncology Immune-pyroptosis Kidney renal clear cell carcinoma Prognosis Biomarkers Pyroptosis |
| title | Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinoma |
| title_full | Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinoma |
| title_fullStr | Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinoma |
| title_full_unstemmed | Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinoma |
| title_short | Immune-pyroptosis-related genes predict the prognosis of kidney renal clear cell carcinoma |
| title_sort | immune pyroptosis related genes predict the prognosis of kidney renal clear cell carcinoma |
| topic | Immune-pyroptosis Kidney renal clear cell carcinoma Prognosis Biomarkers Pyroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323000797 |
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