CTSS in the tumor microenvironment links immune escape and immunotherapy sensitivity in kidney renal clear cell carcinoma.

ABSTRACT: The tumor microenvironment (TME) of kidney renal clear cell carcinoma (KIRC) exhibits complex dynamics among immune, stromal, and malignant cells that drive immune escape (IE) mechanisms and influence clinical outcomes. Through single-cell RNA sequencing and high-dimensional weighted gene co-expression network analysis (hdWGCNA), we identified a crucial IE-related gene module most strongly associated with KIRC progression. Partitioning Around Medoids (PAM) clustering delineated two distinct IE patterns, with pattern one demonstrating prolonged patient survival. Employing advanced machine learning (ML) algorithms, we identified Cathepsin S (CTSS) as the most pivotal tumor suppressor, with elevated CTSS expression consistently predicting improved survival across multiple independent cohorts.

SUBMITTER: Zhou H 

PROVIDER: S-EPMC12307852 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature