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.
Mingyong Li  1 ,  Guoqiang Zhu  1 ,  Yiqi Liu  2 ,  Xuefeng Li  3 ,  Yuxia Zhou  3 ,  Cheng Li  3 ,  Minglei Wang  4 ,  Jin Zhang  5 ,  Zhenping Wang  3 ,  Shuangfeng Tan  3 ,  Wenqi Chen  6 ,  Hu Zhang  1
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.
PMID: 38545181 DOI: 10.1016/j.heliyon.2024.e28295
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.
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