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

• Main Authors: Liu L, Du X, Fang J, Zhao J, Guo Y, Zhao Y, Zou C, Yan X, Li W
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-09-01
• Series: Journal of Inflammation Research
• Subjects: interferon gamma; nomogram; prognostic signature; drug sensitivity; qpcr
• Online Access: https://www.dovepress.com/development-of-an-interferon-gamma-response-related-signature-for-pred-peer-reviewed-fulltext-article-JIR

Lixiao Liu,1,&ast; Xuedan Du,2,&ast; Jintao Fang,3,&ast; Jinduo Zhao,1 Yong Guo,3 Ye Zhao,1 Chengyang Zou,1 Xiaojian Yan,1 Wenfeng Li2 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Urinary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenfeng Li; Xiaojian Yan Email [e-mail]; [e-mail]: 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.Keywords: interferon gamma, nomogram, prognostic signature, drug sensitivity, qPCR