Integrating single-cell and bulk RNA sequencing to identify TXNRD1 as effective target for prognostic and therapeutic strategy in Hepatocellular Carcinoma

Abstract

Abstract Thioredoxin reductase (TXNRD1) acts as part of a major enforcer of redox homeostasis in the intracellular environment. However, its prognostic value and the relationship between TXNRD1 and core ferroptosis-related genes in hepatocellular carcinoma remain unclear. Here, we systematically analyzed and described the potential function and prognostic value of TXNRD1 in hepatocellular carcinoma. TXNRD1 was aberrantly expressed in several cancer types including liver cancer, and elevated TXNRD1 expression was associated with tumor histological grade and pathologic stage, resulting in markedly shorter survival in these patients. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results suggested that TXNRD1 is mainly involved in glucose and fat metabolism. Importantly, TXNRD1 may affect cancer prognosis partially by regulating ferroptosis. A prognostic model based on TXNRD1 and seven ferroptosis-related genes (ATG5, PCBP2, SLC7A11, ACSL6, SAT1, SLC40A1, and STEAP3) divided patients with liver cancer into the low-risk group and the high-risk group and was shown to be an independent risk factor for clinical application. We further found that patients with high-risk scores underwent an increased macrophage infiltration compared to patients with low-risk scores, which resulted in immune escape. In short, TXNRD1 is an overlooked predictor, which can be utilized as a candidate prognostic biomarker in liver cancer, and it may hold promise in drug-resistant patients.