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Pan-Cancer Analysis of Voltage-Dependent Anion Channel (VDAC1) as a Cancer Therapeutic Target or Diagnostic Biomarker
Zhitong Wang1, Yinchu Cheng1, Zaiwei Song1
1Department of Pharmacy, Peking University Third Hospital; Institute for Drug Evaluation, Peking University Health Science Center; Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing 100191, China.
Abstract:
The voltage-dependent anion channel 1 (VDAC1), a pore protein located in the outer mitochondrial membrane, has been confirmed to be related to cancer in cell or animal evidence. However, there is no available pan-cancer analysis of VDAC1. Herein, we investigated the potential roles of VDAC1 in tumorigenesis and progression based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets. The expression of VDAC1 increased in most cancers, and the upregulation of VDAC1 distinctly correlated with the poor prognosis in patients, including breast invasive carcinoma, cervical squamous cell carcinoma, pancreatic adenocarcinoma, lung adenocarcinoma, and skin cutaneous melanoma. We also found VDAC1 S104 phosphorylation raised in various cancers, such as breast cancer, colon cancer, and lung adenocarcinoma. Moreover, the expression of VDAC1 was related to the estimated infiltration value of cancer-associated fibroblasts in bladder urothelial carcinoma, colon adenocarcinoma, kidney renal papillary cell carcinoma, and testicular germ cell tumors. At last, we showed that VDAC1-related oxidative phosphorylation and metabolic regulation may partially explain its association with tumorigenesis and progression. Taken together, this pan-cancer analysis provides relatively comprehensive information on the potential value of VDAC1 as a prognostic biomarker and therapeutic target.
Insights
Voltage-dependent anion channel 1 (VDAC1) is upregulated in most cancers and linked to poor patient prognosis. This pan-cancer analysis highlights VDAC1
Area of Science:
- Mitochondrial biology
- Cancer genomics
- Proteomics
Background:
- Voltage-dependent anion channel 1 (VDAC1) is a mitochondrial outer membrane protein implicated in cancer.
- Previous studies suggest VDAC1's role in cancer, but a comprehensive pan-cancer analysis is lacking.
Purpose of the Study:
- To investigate the potential roles of VDAC1 in tumorigenesis and cancer progression across multiple cancer types.
- To evaluate VDAC1 as a prognostic biomarker and therapeutic target.
Main Methods:
- Utilized data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC).
- Analyzed VDAC1 expression, VDAC1 S104 phosphorylation, and correlation with cancer-associated fibroblasts and patient prognosis.
Main Results:
- VDAC1 expression is increased in most analyzed cancers.
- Upregulated VDAC1 correlates with poor prognosis in specific cancers like breast, cervical, pancreatic, lung, and melanoma.
- VDAC1 S104 phosphorylation is elevated in breast, colon, and lung adenocarcinomas.
- VDAC1 expression is associated with cancer-associated fibroblast infiltration in several tumor types.
- VDAC1-related oxidative phosphorylation and metabolic regulation may contribute to tumorigenesis.
Conclusions:
- VDAC1 is a promising prognostic biomarker and potential therapeutic target in various cancers.
- This pan-cancer analysis provides a comprehensive overview of VDAC1's multifaceted roles in cancer.
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