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Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma

Authors
  • Liu, Lixiao1
  • Du, Xuedan2
  • Fang, Jintao3
  • Zhao, Jinduo1
  • Guo, Yong3
  • Zhao, Ye1
  • Zou, Chengyang1
  • Yan, Xiaojian1
  • Li, Wenfeng2
  • 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang
  • 2 Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang
  • 3 Department of Urinary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang
Type
Published Article
Journal
Journal of Inflammation Research
Publisher
Dove
Publication Date
Sep 27, 2021
Volume
14
Pages
4969–4985
Identifiers
DOI: 10.2147/JIR.S334041
PMID: 34611422
PMCID: PMC8485924
Source
PubMed Central
Keywords
Disciplines
  • Original Research
License
Unknown

Abstract

Background Interferon plays a crucial role in the pathogenesis and progression of tumors. Clear cell renal cell carcinoma (ccRCC) represents a prevalent malignant urinary system tumor. An effective predictive model is required to evaluate the prognosis of patients to optimize treatment. Materials and Methods RNA-sequencing data and clinicopathological data from TCGA were involved in this retrospective study. The IFN-γ response genes with significantly different gene expression were screened out. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to establish a new prognostic scoring model for the training group. Survival curves and ROC curves were drawn, and nomogram was constructed. At the same time, we conducted subgroup analysis and experimental verification using our own samples. Finally, we evaluated the relatedness between the prognostic signature and immune infiltration landscapes. In addition, the sensitivity of different risk groups to six drugs and immune checkpoint inhibitors was calculated. Results The IFN-γ response-related signature included 7 genes: C1S, IFI44, ST3GAL5, NUP93, TDRD7, DDX60, and ST8SIA4. The survival curves of the training and testing groups showed the model’s effectiveness (P = 4.372e-11 and P = 1.08e-08, respectively), the ROC curves showed that the signature was stable, and subgroup analyses showed the wide applicability of the model (P<0.001). Multivariate Cox regression analysis showed that the risk model was an independent prognostic factor of ccRCC. A high-risk score may represent an immunosuppressive microenvironment, while the high-risk group exhibited poor sensitivity to drugs. Conclusion Our findings strongly indicate that the IFN-γ response-related signature can be used as an effective prognostic indicator of ccRCC.

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