Integrated transcriptomic and immunogenomic analysis unravels the immunological functions and prognostic landscape of WD repeat domain 76 - read online free

Sep 22, 2026

Background: WD Repeat Domain 76 (WDR76) is implicated in cellular regulation, yet its cross-cancer landscape and specific biological function in hepatocellular carcinoma (HCC) remain insufficiently characterized. Methods: Multi-omics pan-cancer analyses using TCGA, GTEx, and CCLE assessed expression, subcellular localization, clinicopathologic associations, genomic instability, and immune infiltration; diagnostic/prognostic value used ROC and Kaplan-Meier approaches. Functional validation in HCC used siRNA knockdown in Hep-3B and Huh7 cells. Results: WDR76 was upregulated across tumor types with nuclear localization, linked to advanced stage, metastasis, poor outcomes, immune features, and genomic instability, while correlating with drug resistance. Experimental silencing suppressed proliferation, migration, and invasion. Conclusion: WDR76 serves as a pan-cancer prognostic biomarker and potential immunotherapeutic target.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

Cancer overview

WDR76 rationale and prior evidence

Original research article | Integrated transcriptomic and immunogenomic analysis unravels the immunological functions and prognostic landscape of WD repeat domain 76 | International Journal of
Immunopathology and Pharmacology Volume 40: 1–21 © The Author(s) 2026 Article reuse guidelines:
[sagepub.com/journals-permissions](sagepub.com/journals-permissions)
[DOI: 10.1177/03946320261486727](DOI: 10.1177/03946320261486727)
[journals.sagepub.com/home/iji](journals.sagepub.com/home/iji)

| | --- | --- | | Yifan Wang1,2, Rong Zhou1,2, Shenglong Guo1,2, Shaoting Nan1,2, Yanlong Duan1,2, Lei Cao1,2, Xiujuan Huang3, and Hailong Yan4
Abstract
Background: WD Repeat Domain 76 (WDR76) plays a potential role in cellular regulation; however, its comprehensive landscape across human malignancies and its specific biological function in hepatocellular carcinoma (HCC) remain largely unexplored. Methods: We conducted a systematic pan-cancer analysis utilizing multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) atabases to evaluate WDR76 expression, subcellular localization, and its correlation with clinicopathologic features, genomic instability, and immune infiltration. Diagnostic and prognostic values were assessed via Receiver operating characteristic (ROC) and KaplanMeier analyses. Furthermore, the functional role of WDR76 in HCC was validated in vitro using Hep-3B and Huh7 cell lines through siRNA-mediated knockdown, followed by CCK-8, wound-healing, and transwell assays. Results: WDR76 was significantly upregulated in the majority of tumor types, including LIHC, LUAD, and COAD, while exhibiting nuclear localization. Elevated WDR76 expression correlated with advanced tumor staging, metastasis, and poor clinical outcomes across multiple cohorts, particularly inACC, KIRP, and LIHC. ROC analysis highlighted its exceptional diagnostic precision in cancers such as GBM and LIHC. Immunologically, WDR76 expression was intricately linked to immune cell infiltration, immune checkpoint markers, and genomic instability parameters, suggesting a rolein shaping the tumor microenvironment. Drug sensitivity profiling revealed that high WDR76 levels correlate with resistance to specific chemotherapeutic agents. Experimentally, silencing WDR76 in HCC cells significantly suppressed cell proliferation, migration, and invasion capabilities. Conclusion: Our study establishes WDR76 as a robust pan-cancer prognostic biomarker and a potential immunotherapeutic target. Specifically, we provide experimental evidence that WDR76 functions as an oncogenic driver in liver cancer, promoting malignant phenotypes and offering a novel avenue for targeted therapeutic intervention.
Keywords
WDR76, pan-cancer, cancer biology, immune microenvironment | | | 1Department of Neurology, Shaanxi Provincial People’s Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China 2Department of Geriatric, Shaanxi Provincial People’s Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China 3Department of Hematology, Shaanxi Provincial People’s Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China 4Department of Emergency Surgery, Shaanxi Provincial People’s Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
Corresponding author:
Hailong Yan, Department of Emergency Surgery, Shaanxi Provincial People’s Hospital, Xi’an Jiaotong University, \#No 256, Youyi West Road, Beilin District, Xi’an, Shaanxi Province 710068, China.
Email: [yanhailong2955@163.com](yanhailong2955@163.com) | | Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attri

FAQs

What was the main purpose of the study on WDR76?

The study aimed to define WDR76’s pan-cancer immunological role and prognostic landscape, with particular focus on its biological function in hepatocellular carcinoma (HCC).

How did the researchers evaluate WDR76 clinically and diagnostically?

They used pan-cancer multi-omics datasets (TCGA, GTEx, CCLE) and assessed associations with clinicopathologic features, genomic instability, and immune infiltration, then quantified diagnostic and prognostic performance using ROC and Kaplan-Meier analyses.

What experimental evidence supports WDR76’s role in HCC?

Silencing WDR76 in Hep-3B and Huh7 cells via siRNA suppressed cell proliferation, migration, and invasion, using CCK-8, wound-healing, and transwell assays.

Sep 22, 2026

Upload by CatatanPagi