Based on disulfidptosis, revealing the prognostic and immunological characteristics of renal cell carcinoma with tumor thrombus of vena cava and identifying potential therapeutic target AJAP1.

Abstract

Patients with clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus have a poor prognosis, high surgical risk, and lack of targeted therapeutic agents. Genes with consistent differential expression trends in tumor tissues and VTT groups were first screened, and then differential genes associated with disulfidptosis were found by correlation analysis. Subsequently, identifying ccRCC subtypes and constructing risk models to compare the differences in prognosis and the tumor microenvironment in different subgroups. Finally, constructing a nomogram to predict the prognosis of ccRCC and validate key gene expression levels in cells and tissues. We screened 35 differential genes related to disulfidptosis and identified 4 ccRCC subtypes. Risk models were constructed based on the 13 genes, and the high-risk group had a higher abundance of immune cell infiltration, tumor mutational load, and microsatellite instability scores, predicting high sensitivity to immunotherapy. The 1-year AUC = 0.869 for predicting OS by nomogram has a high application value. The expression level of the key gene AJAP1 was low in both tumor cell lines and cancer tissues. Our study not only constructed an accurate prognostic nomogram for ccRCC patients but also identified an AJAP1 biomarker as a potential biomarker for the disease.