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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Identification of anoikis-related subtypes and immune landscape in kidney renal clear cell carcinoma
Wencong Ding1, Min Zhang1, Ping Zhang1
1The Department of Nephrology and Hemopurification Center, Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong, China.
Abstract:
Anoikis is a specific form of programmed cell death induced by the loss of cell contact with the extracellular matrix and other cells, and plays an important role in organism development, tissue homeostasis, disease development and tumor metastasis. We comprehensively investigated the expression patterns of anoikis-related genes (ARGs) in kidney renal clear cell carcinoma (KIRC) from public databases. Anoikis-related prognostic signatures were established based on four ARGs expression, in which KIRC patients were assigned different risk scores and divided into two different risk groups. In addition, four ARGs expression was validated by qRT-PCR. A better prognosis was observed in the low-risk group, but with lower immune activity (including immune cells and immune-related functions) in the tumor microenvironment. Combined with the relevant clinical characteristics, a nomogram for clinical application was established. Receiver operating characteristics (ROC) and calibration curves were constructed to demonstrate the predictive power of this risk signature. In addition, higher risk scores were significantly and positively correlated with higher gene expression of tumor mutation load (TMB), immune checkpoints (ICPs) and mismatch repair (MMR)-related proteins in general. The results also suggested that the high-risk group was more sensitive to immunotherapy and certain chemotherapeutic agents. Anoikis-related prognostic signatures may provide a better understanding of the roles of ARGs and offer new perspectives for clinical prognosis and individualized treatment.
Insights
Anoikis-related genes (ARGs) can predict kidney cancer prognosis. A new signature identifies patient risk groups, guiding personalized immunotherapy and chemotherapy strategies for better outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Anoikis, a programmed cell death, is crucial for development, homeostasis, and cancer metastasis.
- Understanding anoikis-related genes (ARGs) is vital for kidney renal clear cell carcinoma (KIRC) research.
Purpose of the Study:
- To investigate ARG expression patterns in KIRC.
- To establish an ARG-based prognostic signature for KIRC patients.
- To explore the relationship between ARG signatures and tumor microenvironment, clinical characteristics, and treatment sensitivity.
Main Methods:
- Comprehensive analysis of public database expression patterns for ARGs.
- Development and validation of a four-ARG prognostic signature using qRT-PCR.
- Correlation analysis with tumor mutation load, immune checkpoints, and mismatch repair proteins.
- Nomogram construction for clinical application.
Main Results:
- A prognostic signature based on four ARGs was established, dividing KIRC patients into low- and high-risk groups.
- The low-risk group showed better prognosis but lower immune activity.
- Higher risk scores correlated with increased tumor mutation load, immune checkpoints, and mismatch repair proteins.
- The high-risk group demonstrated increased sensitivity to immunotherapy and certain chemotherapies.
Conclusions:
- The developed ARG prognostic signature offers valuable insights into KIRC progression.
- This signature may aid in predicting patient prognosis and guiding individualized treatment strategies, including immunotherapy and chemotherapy.
- Further understanding of ARGs can enhance clinical management of KIRC.
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