Identification of Survival Risk and Immune-Related Characteristics of Kidney Renal Clear Cell Carcinoma

Abstract

Background. Immunity exerts momentous functions in the progression and treatment of kidney renal clear cell carcinoma (KIRC). A better understanding of the relationship between KIRC and immunity may make a great contribution to evaluating the prognosis and immune-related therapeutic response of KIRC. Methods. A series of information such as RNA sequence, clinical data, and tumor mutation burden (TMB) of KIRC patients were downloaded through The Cancer Genome Atlas (TCGA). Next, combining the survival information and gene expression data of TCGA and Gene Expression Omnibus (GEO), we established an immune gene-related prognosis model (IGRPM) and analyzed it. Then we constructed a nomogram which was convenient for clinicians to judge the prognosis of KIRC. Last but not the least, the expressions of some genes used to construct IGRPM in early KIRC, and adjacent normal tissues were verified through real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Perl (strawberry-perl-5.30.0.1-64bit), R software (4.0.3), and GraphPad Prism 7 were used to process the relevant data. Results. The single-sample gene set enrichment analysis (ssGSEA) showed that there were significant differences in StromalScore, ImmuneScore, ESTIMATEScore, TumorPurity, 22 kinds of human immune cells infiltration, and HLA genes expression between high immunity group (Immunity_H) and low immunity group (Immunity_L). The Immunity_H expressed more immune-related genes and enriched more immune-related functions than the Immunity_L. In addition, compared with the low-risk group, the high-risk group had worse survival outcome and higher TMB. Combining IGRPM-based risk characteristic and TMB, we found that low-TMB + low-risk was the most beneficial to the survival outcome of KIRC patients. The risk characteristic based on IGRPM could be used as an independent prognostic factor for KIRC, and the nomogram constructed for evaluating the prognosis of KIRC showed excellent predictive potential. The RT-qPCR results suggested that not all the genes used to construct IGRPM showed differential expression in early KIRC compared with adjacent normal tissues, but all these genes had significant influence on the prognosis of KIRC. Conclusion. These comprehensive immune assessments and survival predictions, integrating multiple aspects of data and clinical information, can provide additional value to the current Tumor Node Metastasis staging system for risk stratification of KIRC and may facilitate the development of KIRC immunotherapy.

Development of a polyamine gene expression score for predicting prognosis and treatment response in clear cell renal cell carcinoma

“…Theoretically, the number of neoantigens that can be recognized by T cells increases with TMB, and immunotherapy improves. However, T cells may be in a dysfunctional state, and the prognoses of patients with high TMB are poor, consistent with the previous study of ccRCC (68,69). Tumor immune escape can better predict the prognosis of patients than TMB and PD-L1, and T cell dysfunction is an important cause of immune escape (70).…”

Identification of apoptosis-related key genes and the associated regulation mechanism in thoracic aortic aneurysm

“…Immune infiltration, immune regulators and TIME were evaluated to study the differences in immune microenvironment characteristics among these distinct apoptosis modification patterns. ImmuneScore, StromalScore, ESTIMATEScore, and TumorPurity were obtained from ESTIMATE algorithms [ 21 ], and ImmuneScore, StromalScore, and ESTIMATEScore were the lowest in C2, while TumorPurity Score was the highest in C2 (Fig. 8 C).…”

Efficacy and safety analysis of chemotherapy combined with immunotherapy compared with standard chemotherapy for advanced biliary tract malignant tumors

“…However, in cancers where CD8 + T cells were not correlated with neoantigen load (prostate, breast, glioma, etc), the ORR was lower in both TMB‐H and TMB‐L patients. In renal clear cell carcinoma, TMB‐H patients had even lower response rates to ICIs than TMB‐L patients 24 . In addition, Xiaofeng Chen et al 23,25 found that TMB‐H in patients with advanced BTC was associated with poor prognosis and poor immunotherapy effectiveness.…”

“…In renal clear cell carcinoma, TMB-H patients had even lower response rates to ICIs than TMB-L patients. 24 In addition, Xiaofeng Chen et al 23,25 found that TMB-H in patients with advanced BTC was associated with poor prognosis and poor immunotherapy effectiveness. Thus, whether TMB-H can be used as a biomarker to predict the therapeutic effect of ICIs in patents with BTC requires further in-depth investigation.…”