Title:The Necroptotic Process-related Signature Predicts Immune Infiltration and Drug Sensitivity in Kidney Renal Papillary Cell Carcinoma
Volume: 25
Issue: 3
Author(s): Wenfeng Lin, Ruizhi Xue, Hideo Ueki and Peng Huang*
Affiliation:
- Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
- Neutron Therapy Research Center (NTRC), Okayama University, Okayama, Japan
Keywords:
Necroptosis, gene signature, prognosis, immune infiltration, drug sensitivity, kidney renal papillary cell carcinoma.
Abstract:
Background: It remains controversial whether the current subtypes of kidney renal papillary
cell carcinoma (KIRP) can be used to predict the prognosis independently.
Objective: This observational study aimed to identify a risk signature based on necroptotic process-
related genes (NPRGs) in KIRP.
Methods: In the training cohort, LASSO regression was applied to construct the risk signature
from 158 NPRGs, followed by the analysis of Overall Survival (OS) using the Kaplan-Meier
method. The signature accuracy was evaluated by the Receiver Operating Characteristic (ROC)
curve, which was further validated by the test cohort. Wilcoxon test was used to compare the expressions
of immune-related genes, neoantigen genes, and immune infiltration between different
risk groups, while the correlation test was performed between NPRGs expressions and drug sensitivity.
Gene set enrichment analysis was used to investigate the NPRGs' signature’s biological
functions.
Results: We finally screened out 4-NPRGs (BIRC3, CAMK2B, PYGM, and TRADD) for constructing
the risk signature with the area under the ROC curve (AUC) reaching about 0.8. The risk
score could be used as an independent OS predictor. Consistent with the enriched signaling, the
NPRGs signature was found to be closely associated with neoantigen, immune cell infiltration,
and immune-related functions. Based on NPRGs expressions, we also predicted multiple drugs potentially
sensitive or resistant to treatment.
Conclusion: The novel 4-NPRGs risk signature can predict the prognosis, immune infiltration,
and therapeutic sensitivity of KIRP.
