Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer

  • Chi Young Kim (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Eun Hye Lee (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Se Hyun Kwak (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Sang Hoon Lee (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Eun Young Kim (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Min Kyoung Park (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Yoon Jin Cha (Department of Pathology, Yonsei University College of Medicine) ;
  • Yoon Soo Chang (Department of Internal Medicine, Yonsei University College of Medicine)
  • Received : 2023.11.02
  • Accepted : 2024.08.06
  • Published : 2024.10.31
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Abstract

Background: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. Methods: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. Results: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. Conclusion: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

Keywords

Acknowledgement

This study was supported by a faculty research grant from Yonsei University College of Medicine (6-2023-0139). Additionally, this work received support from the NRF grant NRF-2023R1A2C1003235, awarded to Yoon Soo Chang.

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