Systematic analysis of the prognostic value and immunological function of LTBR in human cancer

Sep 21, 2026

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Lymphotoxin beta receptor (LTBR) acts as a positive regulator of T cell proliferation and is closely linked to the tumor immune microenvironment, yet its cancer and immunotherapy roles remain unclear. This study systematically evaluates LTBR expression and prognostic impact across clinical stages, immune and molecular subtypes, and correlates it with immune regulatory, checkpoint, and RNA modification genes. Associations are further tested with immune cells, immune and methylation scores, tumor stemness, MMR genes, DNA methyltransferase, mutation status, TMB, MSI, and pan-cancer functional pathways using GO, KEGG, and GSEA, alongside validation by qRT-PCR and Western blot. Finally, LTBR-targeting drugs are identified; results show overexpression in multiple cancers, low survival, immune-linked infiltration, and enrichment in apoptosis and necroptosis pathways.

LanguageEnglish

CategoryResearch & Report

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Pages24

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ABSTRACT

INTRODUCTION

[www.aging-us.com](www.aging-us.com) AGING 2024, Vol. 16, No. 1 Research Paper Systematic analysis of the prognostic value and immunological function of LTBR in human cancer Yinteng Wu1,*, Shijian Zhao2,*, Wenliang Guo3,*, Ying Liu4, Marìa Del Mar Requena Mullor5, Raquel Alarcòn Rodrìguez5, Ruqiong Wei4 1 Department of Orthopedic and Trauma Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China 2 Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China 3 Department of Rehabilitation Medicine, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi 537100, China 4 Department of Rehabilitation Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China 5 Faculty of Health Sciences, University of Almerìa, La Cañada 04120, Almeria, Spain * Equal contribution Correspondence to: Ruqiong Wei; email: [ruqiongwei@sr.gxmu.edu.cn](ruqiongwei@sr.gxmu.edu.cn) Keywords: lymphotoxin beta receptor (LTBR), pan-cancer, immune microenvironment, T cell, drug sensitivity Received: April 12, 2023 Accepted: November 15, 2023 Published: January 3, 2024 Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Lymphotoxin beta receptor (LTBR) is a positive T cell proliferation regulator gene. It is closely associated with the tumor immune microenvironment. However, its role in cancer and immunotherapy is unclear. Firstly, the expression level and prognostic value of LTBR were analyzed. Secondly, the expression of LTBR in clinical stages, immune subtypes, and molecular subtypes was analyzed. The correlation between LTBR and immune regulatory genes, immune checkpoint genes, and RNA modification genes was then analyzed. Correlations between LTBR and immune cells, scores, cancer-related functional status, tumor stemness index, mismatch repair (MMR) genes, and DNA methyltransferase were also analyzed. In addition, we analyzed the role of LTBRin DNA methylation, mutational status, tumor mutation burden (TMB), and microsatellite instability (MSI). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the role of LTBR in pan-cancer. Finally, the drugs associated with LTBR were analyzed. The expression of LTBR was confirmed using quantitative real-time PCR and Western blot. LTBR is significantly overexpressed in most cancers and is associated with low patient survival. In addition, LTBR expression was strongly correlated with immune cells, score, cancer-related functional status, tumor stemness index, MMR genes, DNA methyltransferase, DNA methylation, mutational status, TMB, and MSI. Enrichment analysis revealed that LTBR was associated with apoptosis, necroptosis, and immune-related pathways. Finally, multiple drugs targeting LTBR were identified. LTBR is overexpressed in several tumors and is associated with a poor prognosis. It is related to immune-related genes and immune cell infiltration. INTRODUCTION Each aspect of the immune system is deeply involved in cancer development and progression [1] . Molecularly targeted therapies are advancing rapidly, and transcriptional analysis provides significant opportunities to understand the complexity of tumors, includingthe tumor microenvironment (TME), which plays a crucial role in cancer progression and treatment [2, 3] . Tumor-infiltrating immune cells have the ability to exert both pro- and antitumor effects, significantly impacting tumor progression and the efficacy of anticancer therapy [4, 5] . Immunotherapy has emerged asa promising approach for advanced cancers, offering breakthrough potential i

FAQs

What is LTBR, and why is it important in cancer research?

LTBR is a positive T cell proliferation regulator gene associated with the tumor immune microenvironment. Its specific roles in cancer progression and immunotherapy response require clarification.

How does the study assess LTBR across tumors?

It analyzes LTBR expression and prognostic value, examines differences across clinical stages and multiple molecular/immune subtypes, and evaluates relationships with immune-related gene sets, immune cells, methylation-related features, and mutational markers such as TMB and MSI.

What main findings connect LTBR with outcomes and immune biology?

LTBR is significantly overexpressed in many cancers and correlates with low patient survival. It is strongly associated with immune cell infiltration and immune-related pathways, including apoptosis and necroptosis, and the study identifies drugs targeting LTBR.

Sep 21, 2026

Uploaded by Logic