ArticleCancer science2020
Ubiquitin C-terminal hydrolase-L1 has prognostic relevance and is a therapeutic target for high-grade neuroendocrine lung cancers.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- The Emerging Role of UCHL1 in Neurological and Musculoskeletal Diseases.Immunology and cell biology · 2026Review
- Spatial transcriptomics reveals molecular heterogeneity and subtype-specific therapeutic targets in small cell lung cancer.NPJ precision oncology · 2026Article
- Proteomics analysis of serum extracellular vesicle identifies UCHL1 as a potential therapeutic target for high grade serous ovarian cancer.British journal of cancer · 2026Article
- UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer.Tuberculosis and respiratory diseases · 2024Article
- UCHL1 is a potential molecular indicator and therapeutic target for neuroendocrine carcinomas.Cell reports. Medicine · 2024Article
- Ubiquitin C‑terminal hydrolase‑L1: A new cancer marker and therapeutic target with dual effects (Review).Oncology letters · 2023Review
- Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness.Cancer cell · 2023Article
- Ubiquitin C-terminal hydrolase L1 promotes lymph node metastasis in small cell neuroendocrine carcinomas of the cervix.The Journal of international medical research · 2022Article
- Integrated analysis of transcription factor-mRNA-miRNA regulatory network related to immune characteristics in medullary thyroid carcinoma.Frontiers in immunology · 2022Article
- Review
- Optimization and Anti-Cancer Properties of Fluoromethylketones as Covalent Inhibitors for Ubiquitin C-Terminal Hydrolase L1.Molecules (Basel, Switzerland) · 2021Article
- Ubiquitin C-terminal hydrolase-L1 has prognostic relevance and is a therapeutic target for high-grade neuroendocrine lung cancers.Cancer science · 2020Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
High-grade neuroendocrine lung cancer (HGNEC), which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is a rapidly proliferating, aggressive form of lung cancer. The initial standard chemotherapeutic regimens of platinum doublets are recommended for SCLC and have been frequently used for LCNEC. However, there are currently no molecularly targeted agents with proven clinical benefit for this disease. The deubiquitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCHL1) is a neuroendocrine cell-specific product that is known as a potential oncogene in several types of cancer, but little is known about the biological function of UCHL1 and its therapeutic potential in HGNEC. In this study, we found that preclinical efficacy evoked by targeting UCHL1 was relevant to prognosis in HGNEC. UCHL1 was found to be expressed in HGNEC, particularly in cell lines and patient samples of SCLC, and the combined use of platinum doublets with selective UCHL1 inhibitors improved its therapeutic response in vitro. Immunohistochemical expression of UCHL1 was significantly associated with postoperative survival in patients with HGNEC and contributed towards distinguishing SCLC from LCNEC. Circulating extracellular vesicles (EV), including exosomes isolated from lung cancer cell lines and serum from early-stage HGNEC, were verified by electron microscopy and nanoparticle tracking analysis. Higher levels of UCHL1 mRNA in EV were found in the samples of patients with early-stage HGNEC than those with early-stage NSCLC and healthy donors' EV. Taken together, UCHL1 may be a potential prognostic marker and a promising druggable target for HGNEC.
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