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

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.

Identifying the role of transient receptor potential channels (TRPs) in kidney renal clear cell carcinoma and their potential therapeutic significances using genomic and transcriptome analyses

“…Urocortin (UCN), belonging to the corticotropin-releasing hormone (CRH) family, is involved in an immune-related signature in the clear cell renal cell carcinoma (ccRCC or KIRC) [33]. Interferoninduced protein 44 (IFI44), as one of the interferon-αstimulated genes, was included in an Interferon Gamma response-related model and an apoptosis-related model for survival prediction in ccRCC [34,35]. HHLA2, with the ability to hinder the human CD4 T-cells and CD8 T-cells proliferation and cytokine production [36], was regarded as a prognostic biomarker and therapeutic target in ccRCC [37][38][39].…”

The IFN-γ-related long non-coding RNA signature predicts prognosis and indicates immune microenvironment infiltration in uterine corpus endometrial carcinoma

“…Liu et al. constructed an IFN-γ-related signature in renal clear cell carcinoma, where the high risk score is associated with immunosuppressive microenvironment and drug resistance ( 52 ). In addition, there are many new signatures being built in multiple tumors.…”

Complement C1s as a diagnostic marker and therapeutic target: Progress and propective

“…Given the close association of complement with immunity, it is not unexpected that activation of C1 is associated with the development, progression, metastasis, and treatment of a variety of cancers ( 50 , 51 ). In clear cell renal cell carcinoma, local production and activation of C1s drove tumor progression and was associated with poor prognosis ( 52 ). Further explorations suggested that C1s facilitates the cancer progression by triggering complement activation, and by modulating the tumor cell phenotype and tumor microenvironment in a complement cascade independent manner ( 53 ).…”