Association of B cells and the risk of Esophageal cancer - a bidirectional two-sample mendelian randomization study

Sep 21, 2026

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Research on the role of B cells in esophageal cancer (EC) remains limited and existing findings are inconsistent. This study disentangles complex causal relationships between B-cell traits and EC. Bidirectional two-sample Mendelian randomization assessed causal links between 190 B-cell phenotypes and EC, complemented by Bayesian Weighted Mendelian Randomization and sensitivity analyses. Findings were validated in independent cohorts and supported with TCGA RNA-seq, including B cell-related gene expression and functional enrichment.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Introduction

Background on esophageal cancer subtypes and prognosis

Motivation for causal and immunology-focused biomarker research

Methods

Bidirectional two-sample Mendelian randomization

Bayesian Weighted Mendelian Randomization and sensitivity analyses

Cohort and TCGA RNA-seq validation

Results

Primary causal associations between B-cell phenotypes and EC

Replication in independent cohorts

RNA-seq expression and functional enrichment findings

Conclusions

Guo et al. BMC Cancer (2024) 24:1416 BMC Cancer [https://doi.org/10.1186/s12885-024-13166-w](https://doi.org/10.1186/s12885-024-13166-w) RESEARCH Open Access Association of B cells and the risk of Esophageal cancer: a bidirectional twosample mendelian randomization study Jinzhou Guo 1,2,3†, Gao Si4†, Xuejie Song 1,2,3 and Fuchun Si 1,2,3* Abstract Background and objectives Currently, research on the role of B cells in esophageal cancer (EC) is limited, and existing studies on their impact are controversial. Therefore, this study was conducted to elucidate the complex causal relationship between B cells and EC, expand the understanding of esophageal cancer immunology. Methods Bidirectional two-sample Mendelian randomization (MR) was performed to assess the causal relationships between 190 B cell phenotypes and EC. To complement the MR analysis, Bayesian Weighted Mendelian Randomization (BWMR) was employed, and sensitivity analyses were conducted to evaluate the robustness of the findings. Positive results were further validated in independent cohorts of esophageal cancer studies. In addition, RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) were utilized for validation, incorporating B cellrelated gene expression analysis and functional enrichment analysis to support the MR findings. Results In the primary analysis, significant causal relationships were observed between 5 B cell types and the risk of EC; the onset of EC was causally linked to 3 B cell phenotypes. Validation in other cohorts revealed that 4 outcomes aligned with the primary analysis, included were CD19 on IgD + CD38-, CD20 on IgD-CD27-, CD20 on IgD-CD38br, and CD38 on PB/PC. Further validation using RNA-seq data showed that CD38 mRNA was significantly overexpressed in EC tissues, whereas CD19 and MS4A1 mRNA levels did not differ significantly between tumor and normal tissues. Functional enrichment analysis revealed that CD19, MS4A1, and CD38 are involved in multiple tumor-related immune pathways, suggesting their pivotal role in regulating the tumor immune microenvironment. Conclusions Our study suggests a potential connection between B cell phenotypes and EC through bidirectional two-sample MR combined with BWMR analysis, providing a preliminary basis for future research. Keywords Esophageal cancer, Immunology, B cells, Causal inference, MR analysis, BWMR analysis †Jinzhou Guo and Gao Si contributed equally to this work. *Correspondence: Fuchun Si [sifc2000@hotmail.com](sifc2000@hotmail.com) 1Academy of Zhongjing, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China 2Laboratory of TCM Syndrome and Prescription Signaling, Academy of zhongjing, Zhengzhou, China 3Henan Key Laboratory of TCM Syndrome and Prescription Signaling, Henan International Joint, Zhengzhou, China 4Department of Orthopedic, Peking University Third Hospital, Beijing, China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd

FAQs

Why were B cells investigated in relation to esophageal cancer?

Prior studies on B-cell roles in esophageal cancer are limited and controversial, motivating a clearer causal evaluation of how B-cell phenotypes relate to EC risk and onset.

What approach was used to assess causal relationships?

The study used bidirectional two-sample Mendelian randomization to test causal links between 190 B-cell phenotypes and EC, further complemented by Bayesian Weighted Mendelian Randomization plus sensitivity analyses.

How were the findings validated?

Results were validated in independent cohorts of esophageal cancer studies, and TCGA RNA-seq data were used to examine B cell-related gene expression and perform functional enrichment analyses to support the MR findings.

Sep 21, 2026

Uploaded by Eden