Evaluation of ENPP1 Expression and Immune Response in Bladder Cancer Patients

NCT ID: NCT06657755

Last Updated: 2024-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

12 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-06-01

Study Completion Date

2024-10-20

Brief Summary

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This study aims to investigate the role of ENPP1 in bladder cancer (BC), specifically focusing on its impact on immune evasion, chemoresistance, and prognosis. The study will analyze gene expression data from clinical samples and use various laboratory techniques, including RNA sequencing, qRT-PCR, and immunohistochemistry, to assess ENPP1's expression levels. In addition, the research will explore the relationship between ENPP1 and immune cell infiltration, along with its correlation with patient survival outcomes. By identifying ENPP1's contribution to cancer progression and treatment resistance, the study aims to discover potential therapeutic targets for improving bladder cancer treatment strategies.

Detailed Description

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This study is designed to comprehensively explore the role of ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1) in bladder cancer (BC) development and progression. ENPP1 has been implicated in various cancers, with evidence suggesting its involvement in immune evasion, chemoresistance, and poor prognosis. However, its specific function in bladder cancer remains unclear. This research will analyze clinical samples, including tumor tissues and normal adjacent tissues, to evaluate ENPP1 expression through a combination of advanced laboratory techniques such as RNA sequencing, quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and immunofluorescence.

Furthermore, the study will investigate the association between ENPP1 expression and key clinical parameters, including tumor stage, grade, lymph node involvement, metastasis, and patient survival outcomes. Through bioinformatics tools, immune infiltration analysis will be conducted to assess the impact of ENPP1 on immune cells such as CD8+ T cells, dendritic cells, and M2 macrophages, which are crucial in the tumor microenvironment.

The research will also explore the correlation between ENPP1 expression and resistance to common chemotherapeutic agents, particularly gemcitabine and cytarabine, using drug sensitivity data from public databases. By identifying the molecular mechanisms by which ENPP1 influences immune responses and chemoresistance, the study aims to provide valuable insights into potential therapeutic targets for bladder cancer treatment. Ultimately, this research may contribute to the development of personalized therapies for bladder cancer patients based on ENPP1 expression.

Conditions

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Bladder (Urothelial, Transitional Cell) Cancer

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

RETROSPECTIVE

Interventions

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Immunohistochemistry

This intervention will specifically focus on evaluating the role of ENPP1 in bladder cancer patients, distinguishing it from other interventions by targeting immune evasion and chemoresistance pathways. The intervention will include a combination of targeted molecular therapies and immunotherapy, aimed at assessing the therapeutic potential of ENPP1 inhibition in improving treatment outcomes for bladder cancer patients. This differs from previous studies by integrating advanced biomarker analysis and personalized treatment approaches based on ENPP1 expression levels.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Adults aged 18 years or older.
* Histologically confirmed diagnosis of bladder cancer.
* Measurable disease as per RECIST criteria.
* Adequate organ function as defined by laboratory tests (e.g., liver, kidney, and hematologic function).
* ENPP1 expression level determined via biopsy or previous analysis.
* Written informed consent provided.

Exclusion Criteria

* History of other malignancies within the past 5 years, excluding non-melanoma skin cancer or in situ carcinoma.
* Prior treatment with ENPP1 inhibitors or similar targeted therapies.
* Active or uncontrolled infections.
* Pregnant or breastfeeding women.
* Known autoimmune disorders or conditions requiring immunosuppressive therapy.
* Inability to comply with the study protocol or procedures.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lanzhou University Second Hospital

OTHER

Sponsor Role lead

Responsible Party

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Chengyu You

Lanzhou University Second Hospital

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Zhilong Dong, MD

Role: STUDY_DIRECTOR

Lanzhou University Second Hospital

Locations

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Lanzhou University Second Hospital

Lanzhou, Gansu, China

Site Status

Countries

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China

References

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An Y, Zhu J, Xie Q, Feng J, Gong Y, Fan Q, Cao J, Huang Z, Shi W, Lin Q, Wu L, Yang C, Ji T. Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling. Adv Sci (Weinh). 2024 May;11(20):e2308131. doi: 10.1002/advs.202308131. Epub 2024 Mar 18.

Reference Type BACKGROUND
PMID: 38498770 (View on PubMed)

Li J, Duran MA, Dhanota N, Chatila WK, Bettigole SE, Kwon J, Sriram RK, Humphries MP, Salto-Tellez M, James JA, Hanna MG, Melms JC, Vallabhaneni S, Litchfield K, Usaite I, Biswas D, Bareja R, Li HW, Martin ML, Dorsaint P, Cavallo JA, Li P, Pauli C, Gottesdiener L, DiPardo BJ, Hollmann TJ, Merghoub T, Wen HY, Reis-Filho JS, Riaz N, Su SM, Kalbasi A, Vasan N, Powell SN, Wolchok JD, Elemento O, Swanton C, Shoushtari AN, Parkes EE, Izar B, Bakhoum SF. Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis. Cancer Discov. 2021 May;11(5):1212-1227. doi: 10.1158/2159-8290.CD-20-0387. Epub 2020 Dec 28.

Reference Type BACKGROUND
PMID: 33372007 (View on PubMed)

Bageritz J, Puccio L, Piro RM, Hovestadt V, Phillips E, Pankert T, Lohr J, Herold-Mende C, Lichter P, Goidts V. Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1. Cell Death Differ. 2014 Jun;21(6):929-40. doi: 10.1038/cdd.2014.12. Epub 2014 Feb 14.

Reference Type BACKGROUND
PMID: 24531536 (View on PubMed)

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

Reference Type BACKGROUND
PMID: 33538338 (View on PubMed)

Related Links

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https://pubmed.ncbi.nlm.nih.gov/33538338/

Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

https://pmc.ncbi.nlm.nih.gov/articles/PMC4013511/

Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1

https://pmc.ncbi.nlm.nih.gov/articles/PMC8102348/

Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis

https://pmc.ncbi.nlm.nih.gov/articles/PMC11132070/

Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling

Other Identifiers

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D2024-686

Identifier Type: OTHER

Identifier Source: secondary_id

2024A-948

Identifier Type: -

Identifier Source: org_study_id

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