Neurogenesis-Associated Protein, a Potential Prognostic Biomarker in Anti-PD-1 Based Kidney Renal Clear Cell Carcinoma Patient Therapeutics

  • 0State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

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Summary

This summary is machine-generated.

Transketolase 1 (TKTL1) impacts kidney cancer prognosis and immune cell infiltration, particularly in clear cell renal cell carcinoma (KIRC). TKTL1 may predict response to anti-PD-1 therapy, with piperine and glibenclamide identified as potential agonists.

Area Of Science

  • Oncology
  • Immunology
  • Pharmacology

Background

  • Transketolase 1 (TKTL1) is crucial for brain development and implicated in cancers.
  • Its role in kidney cancer prognosis and immune cell infiltration is largely unexplored.
  • Understanding TKTL1's function is vital for developing novel kidney cancer therapies.

Purpose Of The Study

  • To investigate TKTL1 expression, its clinical significance, and its association with immune infiltrates in kidney cancer.
  • To explore TKTL1's role in predicting response to anti-PD-1 immunotherapy in renal cancer.
  • To identify and validate TKTL1 agonists for potential therapeutic applications.

Main Methods

  • Utilized various databases and TIMER to analyze TKTL1 expression and immune cell infiltration across cancer types.
  • Performed virtual screening of natural compounds and alkaloids to identify TKTL1 agonists.
  • Conducted in vitro cell viability and colony formation assays to confirm the efficacy of identified agonists.

Main Results

  • TKTL1 expression significantly impacts prognostic potential in kidney cancer subtypes.
  • TKTL1 positively correlates with immune cell infiltration in kidney renal clear cell carcinoma (KIRC), potentially via the mTOR pathway.
  • TKTL1 acts as an immunomodulator in KIRC patients' response to anti-PD-1 therapy.
  • Piperine and glibenclamide were identified as potent TKTL1 agonists, inhibiting Caki-2 cell proliferation in vitro.

Conclusions

  • TKTL1 is a promising prognostic biomarker for KIRC, especially for predicting response to anti-PD-1 therapy.
  • Piperine and glibenclamide demonstrate therapeutic potential as TKTL1 agonists for kidney cancer treatment.
  • This study provides a theoretical basis for utilizing TKTL1 modulation in clinical kidney cancer management.