Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis
IntroductionBladder cancer (BC) is a significant carcinoma of the urinary system that has a high incidence of morbidity and death owing to the challenges in accurately identifying people with early-stage BC and the lack of effective treatment options for those with advanced BC. Thus, there is a need...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1102392/full |
| _version_ | 1797361726766710784 |
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| author | Weifeng Wang Guankai Huang Hansen Lin Hansen Lin Lei Ren Liangmin Fu Liangmin Fu Xiaopeng Mao |
| author_facet | Weifeng Wang Guankai Huang Hansen Lin Hansen Lin Lei Ren Liangmin Fu Liangmin Fu Xiaopeng Mao |
| author_sort | Weifeng Wang |
| collection | DOAJ |
| description | IntroductionBladder cancer (BC) is a significant carcinoma of the urinary system that has a high incidence of morbidity and death owing to the challenges in accurately identifying people with early-stage BC and the lack of effective treatment options for those with advanced BC. Thus, there is a need to define new markers of prognosis and prediction.MethodsIn this study, we have performed a comprehensive proteomics experiment by label-free quantitative proteomics to compare the proteome changes in the serum of normal people and bladder cancer patients—the successful quantification of 2064 Quantifiable proteins in total. A quantitative analysis was conducted to determine the extent of changes in protein species' relative intensity and reproducibility. There were 43 upregulated proteins and 36 downregulated proteins discovered in non-muscle invasive bladder cancer and normal individuals. Sixty-four of these proteins were elevated, and 51 were downregulated in muscle-invasive and non-muscle-invasive bladder cancer, respectively. Functional roles of differentially expressed proteins were annotated using Gene Ontology (GO) and Clusters of Orthologous Groups of Proteins (COG). To analyze the functions and pathways enriched by differentially expressed proteins, GO enrichment analysis, protein domain analysis, and KEGG pathway analysis were performed. The proteome differences were examined and visualized using radar plots, heat maps, bubble plots, and Venn diagrams.ResultsAs a result of combining the Venn diagram with protein-protein interactions (PPIs), Chloride intracellular channel 1 (CLIC1) was identified as the primary protein. Using the Gene Set Cancer Analysis (GSCA) website, the influence of CLIC1 on immune infiltration was analyzed. A negative correlation between CD8 naive and CLIC1 levels was found. For validation, immunohistochemical (IHC), qPCR, and western blotting (WB) were performed.Further, we found that CLIC1 was associated with a poor prognosis of bladder cancer in survival analysis.DiscussionOur research screened CLIC1 as a tumor-promoting protein in bladder cancer for the first time using serum mass spectrometry. And CLIC1 associated with tumor stage, and immune infiltrate. The prognostic biomarker and therapeutic target CLIC1 may be new for bladder cancer patients. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-08T15:57:37Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-7b0c2f04708b4743971562f18123bd032024-01-08T16:27:03ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.11023921102392Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosisWeifeng Wang0Guankai Huang1Hansen Lin2Hansen Lin3Lei Ren4Liangmin Fu5Liangmin Fu6Xiaopeng Mao7Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaInstitute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaInstitute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaIntroductionBladder cancer (BC) is a significant carcinoma of the urinary system that has a high incidence of morbidity and death owing to the challenges in accurately identifying people with early-stage BC and the lack of effective treatment options for those with advanced BC. Thus, there is a need to define new markers of prognosis and prediction.MethodsIn this study, we have performed a comprehensive proteomics experiment by label-free quantitative proteomics to compare the proteome changes in the serum of normal people and bladder cancer patients—the successful quantification of 2064 Quantifiable proteins in total. A quantitative analysis was conducted to determine the extent of changes in protein species' relative intensity and reproducibility. There were 43 upregulated proteins and 36 downregulated proteins discovered in non-muscle invasive bladder cancer and normal individuals. Sixty-four of these proteins were elevated, and 51 were downregulated in muscle-invasive and non-muscle-invasive bladder cancer, respectively. Functional roles of differentially expressed proteins were annotated using Gene Ontology (GO) and Clusters of Orthologous Groups of Proteins (COG). To analyze the functions and pathways enriched by differentially expressed proteins, GO enrichment analysis, protein domain analysis, and KEGG pathway analysis were performed. The proteome differences were examined and visualized using radar plots, heat maps, bubble plots, and Venn diagrams.ResultsAs a result of combining the Venn diagram with protein-protein interactions (PPIs), Chloride intracellular channel 1 (CLIC1) was identified as the primary protein. Using the Gene Set Cancer Analysis (GSCA) website, the influence of CLIC1 on immune infiltration was analyzed. A negative correlation between CD8 naive and CLIC1 levels was found. For validation, immunohistochemical (IHC), qPCR, and western blotting (WB) were performed.Further, we found that CLIC1 was associated with a poor prognosis of bladder cancer in survival analysis.DiscussionOur research screened CLIC1 as a tumor-promoting protein in bladder cancer for the first time using serum mass spectrometry. And CLIC1 associated with tumor stage, and immune infiltrate. The prognostic biomarker and therapeutic target CLIC1 may be new for bladder cancer patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.1102392/fullproteomicsbiology-informed analysisCLIC1prognosisbladder cancer |
| spellingShingle | Weifeng Wang Guankai Huang Hansen Lin Hansen Lin Lei Ren Liangmin Fu Liangmin Fu Xiaopeng Mao Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis Frontiers in Oncology proteomics biology-informed analysis CLIC1 prognosis bladder cancer |
| title | Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis |
| title_full | Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis |
| title_fullStr | Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis |
| title_full_unstemmed | Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis |
| title_short | Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis |
| title_sort | label free lc ms ms proteomics analyses reveal clic1 as a predictive biomarker for bladder cancer staging and prognosis |
| topic | proteomics biology-informed analysis CLIC1 prognosis bladder cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1102392/full |
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