Ferroptosis-related STEAP3 acts as predictor and regulator in diffuse large B cell lymphoma through immune infiltration

• Published in: Clinical and experimental medicine Vol. 23; no. 6; pp. 2601 - 2617
• Main Authors: Chen, Xiaomin, Hu, Shunfeng, Han, Yang, Cai, Yiqing, Lu, Tiange, Hu, Xinting, Chu, Yurou, Zhou, Xiangxiang, Wang, Xin
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-10-2023; Springer Nature B.V
• Subjects: B-cell lymphoma; Cell death; Ferroptosis; Gene expression; Gene set enrichment analysis; Hematology; Immunohistochemistry; Infiltration; Internal Medicine; Lymphoma; Medicine; Medicine & Public Health; Metastases; Microenvironments; mRNA; Oncology; Patients; PD-L1 protein; Prognosis; Risk groups; Tumor cells; Tumors; Western blotting; Ferroptosis; Tumor immune microenvironment; DLBCL; Prognosis; Immunotherapy
• ISSN: 1591-9528; 1591-8890; 1591-9528
• DOI: 10.1007/s10238-023-00996-4

Diffuse large B cell lymphoma (DLBCL) is a usual-seen hematological malignant tumor possessing molecular and genetic heterogeneity. Ferroptosis induction has been increasingly acknowledged to be an advantageous therapeutic method in tumor treatment by triggering cell death of tumor cells. However, studies on the function of ferroptosis in DLBCL remain scarce, especially the interaction with the tumor immune microenvironment (TIME). The clinical and biological functions of ferroptosis-related genes in DLBCL were still warranted to be explored. A ferroptosis-related risk model was constructed, followed by functional enrichment analyses and evaluation of immune profile. Quantitative real-time PCR, western blotting, and immunohistochemistry were conducted to examine the RNA and protein levels. Dysregulated expression of the major ferroptosis-related genes was found in DLBCL. A prognostic risk model based on 10 ferroptosis-related genes was constructed. The risk score served as an independent prognostic indicator for DLBCL patients in univariate and multivariate Cox regression analysis. Patients with low-risk scores presented a more favorable prognosis. Functional enrichment analysis revealed that immune-related pathways were significantly enriched, and the high-risk group exhibited less immunocyte infiltration, lower immunoscore, and downregulated PD-L1 expression relative to the low-risk group. Two molecular subtypes were determined through consensus clustering of the expression of ferroptosis-related genes. Cluster 1 was relevant to favorable prognosis, higher immunoscore, and elevated PD-L1 expression. More importantly, STEAP3 was screened as a reliable biomarker for DLBCL, and its enhanced expression levels of mRNA and protein were verified in public databases and clinical specimens. Our study demonstrated the crucial role of ferroptosis-related genes including STEAP3 in the TIME of DLBCL and identified promising novel molecular targets for DLBCL treatment.