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

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; 2De...

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Autores principales:	Liu L, Du X, Fang J, Zhao J, Guo Y, Zhao Y, Zou C, Yan X, Li W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	interferon gamma nomogram prognostic signature drug sensitivity qpcr Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/9851d772e4fe4f43b754a64530e87f42
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spelling	oai:doaj.org-article:9851d772e4fe4f43b754a64530e87f422021-12-02T15:17:58ZDevelopment of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma1178-7031https://doaj.org/article/9851d772e4fe4f43b754a64530e87f422021-09-01T00:00:00Zhttps://www.dovepress.com/development-of-an-interferon-gamma-response-related-signature-for-pred-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Lixiao 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 liwenfeng@wmu.edu.cn; yxjbetter2016@hotmail.comBackground: 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, qPCRLiu LDu XFang JZhao JGuo YZhao YZou CYan XLi WDove Medical Pressarticleinterferon gammanomogramprognostic signaturedrug sensitivityqpcrPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4969-4985 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	interferon gamma nomogram prognostic signature drug sensitivity qpcr Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	interferon gamma nomogram prognostic signature drug sensitivity qpcr Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Liu L Du X Fang J Zhao J Guo Y Zhao Y Zou C Yan X Li W Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma
description	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 liwenfeng@wmu.edu.cn; yxjbetter2016@hotmail.comBackground: 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
format	article
author	Liu L Du X Fang J Zhao J Guo Y Zhao Y Zou C Yan X Li W
author_facet	Liu L Du X Fang J Zhao J Guo Y Zhao Y Zou C Yan X Li W
author_sort	Liu L
title	Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma
title_short	Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma
title_full	Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma
title_fullStr	Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma
title_full_unstemmed	Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma
title_sort	development of an interferon gamma response-related signature for prediction of survival in clear cell renal cell carcinoma
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/9851d772e4fe4f43b754a64530e87f42
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Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma

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