We have located links that may give you full text access.
Single-cell dissection reveals the role of aggrephagy patterns in tumor microenvironment components aiding predicting prognosis and immunotherapy on lung adenocarcinoma.
Aging 2023 December 14
BACKGROUND: Lung adenocarcinoma (LUAD) is one of the leading malignant cancers. Aggrephagy plays a critical role in key genetic events for various cancers; yet, how aggrephagy functions within the tumor microenvironment (TME) in LUAD remains to be elucidated.
METHODS: In this study, by sequential non-negative matrix factorization (NMF) algorithm, pseudotime analysis, cell-cell interaction analysis, and SCENIC analysis, we have shown that aggrephagy genes demonstrated various patterns among different cell types in LUAD TME. LUAD and Immunotherapy cohorts from public repository were used to determine the prognosis and immune response of aggrephagy TME subtypes. The aggrephagy-deprived prognostic score (ADPS) was quantified based on machine learning algorithms.
RESULTS: The cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and CD8+ T cells have various aggrephagy patterns, which enhance the intensity of intercellular communication and transcription factor activation. Furthermore, based on the signatures of the newly defined aggrephagy cell subtypes and expression profiles of large cohorts in LUAD patients, we determine that DYNC1I2+CAF-C1, DYNLL1+CAF-C2, PARK7+CAF-C3, VIM+Mac-C1, PARK7+Mac-C2, VIM+CD8+T_cells-C1, UBA52+CD8+T_cells-C2, TUBA4A+CD8+T_ cells-C3, and TUBA1A+CD8+T_cells-C4 are crucial prognostic factors for LUAD patients. The developed ADPS could predict survival outcomes and immunotherapeutic response across ten cohorts ( n = 1838), and patients with low ADPS owned a better prognosis, lower genomic alterations, and are more sensitive to immunotherapy. Meanwhile, based on PRISM, CTRP, and CMAP databases, PLK inhibitor BI-2536, may be a potential agent for patients with high ADPS.
CONCLUSIONS: Taken together, our novel and systematic single-cell analysis has revealed the unique role of aggrephagy in remodeling the TME of LUAD. As a newly demonstrated biomarker, the ADPS facilitates the clinical management and individualized treatment of LUAD.
METHODS: In this study, by sequential non-negative matrix factorization (NMF) algorithm, pseudotime analysis, cell-cell interaction analysis, and SCENIC analysis, we have shown that aggrephagy genes demonstrated various patterns among different cell types in LUAD TME. LUAD and Immunotherapy cohorts from public repository were used to determine the prognosis and immune response of aggrephagy TME subtypes. The aggrephagy-deprived prognostic score (ADPS) was quantified based on machine learning algorithms.
RESULTS: The cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and CD8+ T cells have various aggrephagy patterns, which enhance the intensity of intercellular communication and transcription factor activation. Furthermore, based on the signatures of the newly defined aggrephagy cell subtypes and expression profiles of large cohorts in LUAD patients, we determine that DYNC1I2+CAF-C1, DYNLL1+CAF-C2, PARK7+CAF-C3, VIM+Mac-C1, PARK7+Mac-C2, VIM+CD8+T_cells-C1, UBA52+CD8+T_cells-C2, TUBA4A+CD8+T_ cells-C3, and TUBA1A+CD8+T_cells-C4 are crucial prognostic factors for LUAD patients. The developed ADPS could predict survival outcomes and immunotherapeutic response across ten cohorts ( n = 1838), and patients with low ADPS owned a better prognosis, lower genomic alterations, and are more sensitive to immunotherapy. Meanwhile, based on PRISM, CTRP, and CMAP databases, PLK inhibitor BI-2536, may be a potential agent for patients with high ADPS.
CONCLUSIONS: Taken together, our novel and systematic single-cell analysis has revealed the unique role of aggrephagy in remodeling the TME of LUAD. As a newly demonstrated biomarker, the ADPS facilitates the clinical management and individualized treatment of LUAD.
Full text links
Related Resources
Trending Papers
Executive Summary: State-of-the-Art Review: Unintended Consequences: Risk of Opportunistic Infections Associated with Long-term Glucocorticoid Therapies in Adults.Clinical Infectious Diseases 2024 April 11
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.International Journal of Molecular Sciences 2024 April 13
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia 2024 April 13
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app