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Article Open Access

A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma

  • Authors:
    • Gangcheng Liu
    • Donglan Xiong
    • Zhifei Che
    • Hualei Chen
    • Wenyi Jin
  • View Affiliations / Copyright

    Affiliations: Department of Urology Surgery, Affiliated Renhe Hospital of China Three Gorges University Second Clinical Medical College of China Three Gorges University, Yichang, Hubei 443000, P.R. China, Department of Respiratory Medicine, Affiliated Renhe Hospital of China Three Gorges University Second Clinical Medical College of China Three Gorges University, Yichang, Hubei 443000, P.R. China, Department of Urology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570100, P.R. China, Department of Urology Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570100, P.R. China, Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 307
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    Published online on: July 12, 2022
       https://doi.org/10.3892/ol.2022.13427
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Abstract

Clear cell renal cell carcinoma (ccRCC) are typically situated in a complex inflammatory and immune microenvironment, which has been reported to contribute to the unfavorable prognosis of patients with ccRCC. There would be beneficial clinical implications for elucidating the roles of its molecular characteristics in the inflammatory microenvironment. This is because it would facilitate the development of reliable biomarkers for pre‑stratification prior to the designation of individualized treatment strategies. In the present study, RNA‑sequencing data from 607 patients were retrospectively analyzed to elucidate the profile of inflammatory molecules. Based on this, an inflammatory prognostic signature (IPS) was developed and further validated using clinical ccRCC samples. Subsequently, the associated mechanisms in terms of the immune microenvironment and molecular pathways were then investigated. This proposed IPS was found to exhibit superior accuracy compared with the criterion of a good prognostic model for the prediction of patient prognosis from ccRCC [area under the receiver operating characteristic curve (AUC)=0.811] in addition to being an independent factor for prognostic risk stratification [hazard ratio: 11.73 (95% CI, 26.98‑5.10); log‑rank test, P<0.001]. Pathologically, ccRCC cells identified as high‑risk according to their IPS presented with a more malignant tumor structure, including voluminous eosinophilic cytoplasm, acinar/lamellar/tubular growth patterns and atypic nuclei. High‑risk ccRCC also exhibited higher infiltration levels by four types of immune cells, including T regulatory cells, but lower infiltration levels by mast cells. Pathways associated with immune‑inflammation interaction, including the IL‑17 pathway, were found to be upregulated in IPS‑identified high‑risk ccRCC. Furthermore, by combining the IPS with clinical factors, an integrated prognostic index was developed and validated for increasing the accuracy of patient risk‑stratification for ccRCC (AUC=0.911). In conclusion, the complex regulatory mechanisms and molecular characteristics involved in ccRCC‑inflammation interaction, coupled with their prognostic potential, were systematically elucidated in the present study. This may have important implications in furthering the understanding into the molecular mechanisms underlying this ccRCC‑inflammation interaction, which can in turn be exploited for identifying high‑risk patients with ccRCC prior to designing their clinical treatment strategy.
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Copy and paste a formatted citation
Spandidos Publications style
Liu G, Xiong D, Che Z, Chen H and Jin W: A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma. Oncol Lett 24: 307, 2022.
APA
Liu, G., Xiong, D., Che, Z., Chen, H., & Jin, W. (2022). A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma. Oncology Letters, 24, 307. https://doi.org/10.3892/ol.2022.13427
MLA
Liu, G., Xiong, D., Che, Z., Chen, H., Jin, W."A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma". Oncology Letters 24.3 (2022): 307.
Chicago
Liu, G., Xiong, D., Che, Z., Chen, H., Jin, W."A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma". Oncology Letters 24, no. 3 (2022): 307. https://doi.org/10.3892/ol.2022.13427
Copy and paste a formatted citation
x
Spandidos Publications style
Liu G, Xiong D, Che Z, Chen H and Jin W: A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma. Oncol Lett 24: 307, 2022.
APA
Liu, G., Xiong, D., Che, Z., Chen, H., & Jin, W. (2022). A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma. Oncology Letters, 24, 307. https://doi.org/10.3892/ol.2022.13427
MLA
Liu, G., Xiong, D., Che, Z., Chen, H., Jin, W."A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma". Oncology Letters 24.3 (2022): 307.
Chicago
Liu, G., Xiong, D., Che, Z., Chen, H., Jin, W."A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma". Oncology Letters 24, no. 3 (2022): 307. https://doi.org/10.3892/ol.2022.13427
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