Multi-omics landscape analysis reveals the pan-cancer association of arginine biosynthesis genes with tumor immune evasion and therapy resistance
Zhiyong Tan,
Haihao Li,
Yinglong Huang,
Shi Fu,
Haifeng Wang,
Jiansong Wang
Affiliations
Zhiyong Tan
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Urological disease clinical medical center of Yunnan province, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming 650101, Yunnan, China
Haihao Li
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Urological disease clinical medical center of Yunnan province, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming 650101, Yunnan, China
Yinglong Huang
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Urological disease clinical medical center of Yunnan province, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming 650101, Yunnan, China
Shi Fu
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Urological disease clinical medical center of Yunnan province, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming 650101, Yunnan, China
Haifeng Wang
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Urological disease clinical medical center of Yunnan province, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming 650101, Yunnan, China; Corresponding author. Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming 650101, China.
Jiansong Wang
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Urological disease clinical medical center of Yunnan province, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 347, Dianmian Street, Wuhua District, Kunming 650101, Yunnan, China
Background: The metabolism of arginine, a conditionally essential amino acid, plays a crucial role in cancer progression and prognosis. However, a more detailed understanding of the influence of arginine biosynthesis genes in cancer is currently unavailable. Methods: We performed an integrative multi-omics analysis using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to determine the characteristics of these genes across multiple cancer types. To measure the overall activity of arginine biosynthesis genes in cancer, we calculated arginine biosynthesis scores based on gene expression. Results: Our results indicated that the arginine biosynthesis score was negatively correlated with immune-related pathways, immune infiltration, immune checkpoint expression, and patient prognosis, and single-cell data further clarified that patients with high arginine biosynthesis scores showed a reduced proportion of T and B cells in an immune desert tumor microenvironment and were insensitive to immunotherapy. We also identified several potential drugs through the Cancer Therapeutic Response Portal (CTRP) and Genomics of Drug Sensitivity in Cancer (GDSC) databases that could target arginine biosynthesis genes and potentially improve the response rate to immunotherapy in patients with a high arginine biosynthesis fraction. Conclusion: Overall, our analyses emphasize that arginine biosynthesis genes are associated with immune evasion in several cancers. Targeting these genes may facilitate more effective immunotherapy.
