Integrated genomic and proteomic analyses identify PYGL as a novel experimental therapeutic target for clear cell renal cell carcinoma

Mingyong Li; Guoqiang Zhu; Yiqi Liu; Xuefeng Li; Yuxia Zhou; Cheng Li; Minglei Wang; Jin Zhang; Zhenping Wang; Shuangfeng Tan; Wenqi Chen; Hu Zhang

doi:10.1016/j.heliyon.2024.e28295

Integrated genomic and proteomic analyses identify PYGL as a novel experimental therapeutic target for clear cell renal cell carcinoma

Heliyon. 2024 Mar 16;10(6):e28295. doi: 10.1016/j.heliyon.2024.e28295. eCollection 2024 Mar 30.

Authors

Mingyong Li¹, Guoqiang Zhu¹, Yiqi Liu², Xuefeng Li³, Yuxia Zhou³, Cheng Li³, Minglei Wang⁴, Jin Zhang⁵, Zhenping Wang³, Shuangfeng Tan³, Wenqi Chen⁶, Hu Zhang¹

Affiliations

¹ The First Affiliated Hospital, Department of Urology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
² The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
³ The First Affiliated Hospital, Department of Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
⁴ Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China.
⁵ Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, China.
⁶ Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, University of South China, 421000 Hengyang, Hunan, China.

Abstract

Sunitinib, the first-line targeted therapy for metastatic clear cell renal cell carcinoma (ccRCC), faces a significant challenge as most patients develop acquired resistance. Integrated genomic and proteomic analyses identified PYGL as a novel therapeutic target for ccRCC. PYGL knockdown inhibited cell proliferation, cloning capacity, migration, invasion, and tumorigenesis in ccRCC cell lines. PYGL expression was increased in sunitinib-resistant ccRCC cell lines, and CP-91149 targeting the PYGL could restore drug sensitivity in these cell lines. Moreover, chromatin immune-precipitation assays revealed that PYGL upregulation is induced by the transcription factor, hypoxia-inducible factor 1α. Overall, PYGL was identified as a novel diagnostic biomarker by combining genomic and proteomic approaches in ccRCC, and sunitinib resistance to ccRCC may be overcome by targeting PYGL.

Keywords: PYGL; Resistance; Sunitinib; Target therapy; ccRCC.