Top

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

Journals by subject

Unlock free access to practice-relevant journal articles

Join our community of medical professionals and register now to access a handpicked selection of journal articles from Springer's Medical portfolio.

Editor's Choice | Journals

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest Journal Issues

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Looking for something specific?

Find articles from over 500 clinical journals from Springer with the search function.

Latest issues in Internal Medicine

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Cardiology

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Diabetes & Endocrinology

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Neurology

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Oncology

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Pediatrics

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Respiratory Medicine

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

About journals on Springer Medicine

The range of medical journals on Springer Medicine is extremely diverse. It includes the current editions and archives of around 500 English-language journals from almost all medical disciplines published by Springer.

The specialist literature is usually available both online in full text and as a PDF for download. The online view is optimized in such a way that the specialist texts can be read comfortably on all screen sizes, from desktops to tablets to smartphones. We also include features to support your use of the journals for your research, such as bookmark setting.

Whether you’re interested in internal medicine, surgery, general medicine, gynecology, orthopedics, neurology, or pediatrics, there are excellent journals in almost every subject area, such as the BMC Series, Diabetologia, Breast Cancer Research, Current Obesity Reports, CNS Drugs and many others, all of which are an integral part of the everyday life of doctors across Europe.

The breadth of content from this suite of journals allows the Springer Medicine team to collect and deliver broad-ranging content across the full spectrum of medical knowledge, with a special focus on topics highlighted by these leading journals and their editorial boards and specialist authors. This guarantees a high quality of content and ensures that our readers are offered the most relevant topics in their respective specialist area.

Our experienced clinical content managers constantly monitor the needs of medical professionals to provide up-to-date reports from international congresses, expert interviews, and a range of digestible content on emerging topics in the field of medicine.

BMC Cancer

Published in:

Open Access 01-12-2024 | Research

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

Authors: Jinzhou Guo, Gao Si, Xuejie Song, Fuchun Si

Published in: BMC Cancer | Issue 1/2024

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 cell-related 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.

Available only for authorised users

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.CrossRef

Fan J, Liu Z, Mao X, Tong X, Zhang T, Suo C, et al. Global trends in the incidence and mortality of esophageal cancer from 1990 to 2017. Cancer Med. 2020;9(18):6875–87. https://doi.org/10.1002/cam4.3338.CrossRefPubMed

Sheikh M, Roshandel G, McCormack V, Malekzadeh R. Current status and future prospects for esophageal Cancer. Cancers. 2023;15(3). https://doi.org/10.3390/cancers15030765.

Zou M, Liang Q, Zhang W, Zhu Y, Xu Y. Causal association between dietary factors and esophageal diseases: a mendelian randomization study. PLoS ONE. 2023;18(11):e0292113. https://doi.org/10.1371/journal.pone.0292113.CrossRefPubMedPubMedCentral

Wang W, Ye L, Li H, Chen W, Hong W, Mao W, et al. A narrative review on advances in neoadjuvant immunotherapy for esophageal cancer: molecular biomarkers and future directions. Int J Cancer. 2024. https://doi.org/10.1002/ijc.35153.CrossRefPubMed

Wang Y, Yang W, Wang Q, Zhou Y. Mechanisms of esophageal cancer metastasis and treatment progress. Front Immunol. 2023;14:1206504. https://doi.org/10.3389/fimmu.2023.1206504.CrossRefPubMedPubMedCentral

Lee S, Cohen DJ. Pharmacotherapy for metastatic esophageal cancer: where do we need to improve? Expert opinion on pharmacotherapy 2019; 20, (3):357–66. https://doi.org/10.1080/14656566.2018.1551881

Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol (Baltimore Md: 1950). 2014;192(12):5451–8. https://doi.org/10.4049/jimmunol.1490019.CrossRef

Hernandez R, Põder J, LaPorte KM, Malek TR, Engineering. IL-2 for immunotherapy of autoimmunity and cancer. Nat Rev Immunol. 2022;22(10):614–28. https://doi.org/10.1038/s41577-022-00680-w.CrossRefPubMed

10.

Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17(8):807–21. https://doi.org/10.1038/s41423-020-0488-6.CrossRefPubMedPubMedCentral

11.

Lim JS, Sundar R, Chénard-Poirier M, Lopez J, Yap TA. Emerging biomarkers for PD-1 pathway cancer therapy. Biomark Med. 2017;11(1):53–67. https://doi.org/10.2217/bmm-2016-0228.CrossRefPubMed

12.

Fang P, Zhou J, Liang Z, Yang Y, Luan S, Xiao X, et al. Immunotherapy resistance in esophageal cancer: possible mechanisms and clinical implications. Front Immunol. 2022;13:975986. https://doi.org/10.3389/fimmu.2022.975986.CrossRefPubMedPubMedCentral

13.

Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651–68. https://doi.org/10.1038/s41577-020-0306-5.CrossRefPubMedPubMedCentral

14.

Wouters MCA, Nelson BH. Prognostic significance of Tumor-infiltrating B cells and plasma cells in Human Cancer. Clin cancer Research: Official J Am Association Cancer Res. 2018;24(24):6125–35. https://doi.org/10.1158/1078-0432.ccr-18-1481.CrossRef

15.

Petitprez F, de Reyniès A, Keung EZ, Chen TW, Sun CM, Calderaro J, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020;577(7791):556–60. https://doi.org/10.1038/s41586-019-1906-8.CrossRefPubMed

16.

Helmink BA, Reddy SM, Gao J, Zhang S, Basar R, Thakur R, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020;577(7791):549–55. https://doi.org/10.1038/s41586-019-1922-8.CrossRefPubMedPubMedCentral

17.

Cabrita R, Lauss M, Sanna A, Donia M, Skaarup Larsen M, Mitra S, et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature. 2020;577(7791):561–5. https://doi.org/10.1038/s41586-019-1914-8.CrossRefPubMed

18.

Qin Z, Richter G, Schüler T, Ibe S, Cao X, Blankenstein T. B cells inhibit induction of T cell-dependent tumor immunity. Nat Med. 1998;4(5):627–30. https://doi.org/10.1038/nm0598-627.CrossRefPubMed

19.

Perricone MA, Smith KA, Claussen KA, Plog MS, Hempel DM, Roberts BL et al. Enhanced efficacy of melanoma vaccines in the absence of B lymphocytes. Journal of immunotherapy (Hagerstown, Md: 1997) 2004; 27, (4):273–281. https://doi.org/10.1097/00002371-200407000-00003

20.

Cillo AR, Kürten CHL, Tabib T, Qi Z, Onkar S, Wang T, et al. Immune Landscape of viral- and carcinogen-driven Head and Neck Cancer. Immunity. 2020;52(1):183–e199189. https://doi.org/10.1016/j.immuni.2019.11.014.CrossRefPubMedPubMedCentral

21.

Qin Y, Lu F, Lyu K, Chang AE, Li Q. Emerging concepts regarding pro- and anti tumor properties of B cells in tumor immunity. Front Immunol. 2022;13:881427. https://doi.org/10.3389/fimmu.2022.881427.CrossRefPubMedPubMedCentral

22.

Lu Y, Zhao Q, Liao JY, Song E, Xia Q, Pan J, et al. Complement signals determine Opposite effects of B cells in Chemotherapy-Induced immunity. Cell. 2020;180(6):1081–e10971024. https://doi.org/10.1016/j.cell.2020.02.015.CrossRefPubMed

23.

Li R, Huang X, Yang W, Wang J, Liang Y, Zhang T, et al. Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma. J Pathol Clin Res. 2022;8(5):422–35. https://doi.org/10.1002/cjp2.281.CrossRefPubMedPubMedCentral

24.

Birney E. Mendelian randomization. Cold Spring Harbor Perspect Med. 2022;12(4). https://doi.org/10.1101/cshperspect.a041302.

25.

Chen J, Yuan S, Fu T, Ruan X, Qiao J, Wang X, et al. Gastrointestinal consequences of type 2 diabetes Mellitus and impaired glycemic homeostasis: a mendelian randomization study. Diabetes Care. 2023;46(4):828–35. https://doi.org/10.2337/dc22-1385.CrossRefPubMedPubMedCentral

26.

Davies NM, Holmes MV, Davey Smith G. Reading mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ (Clinical Res ed). 2018;362:k601. https://doi.org/10.1136/bmj.k601.CrossRef

27.

Zhao J, Ming J, Hu X, Chen G, Liu J, Yang C. Bayesian weighted mendelian randomization for causal inference based on summary statistics. Bioinf (Oxford England). 2020;36(5):1501–8. https://doi.org/10.1093/bioinformatics/btz749.CrossRef

28.

Orrù V, Steri M, Sidore C, Marongiu M, Serra V, Olla S, et al. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet. 2020;52(10):1036–45. https://doi.org/10.1038/s41588-020-0684-4.CrossRefPubMedPubMedCentral

29.

Yang Q, Duan B, Yue J, Zhang D, Chen X, Shi M, et al. Causal effects and metabolites mediators between immune cell and risk of colorectal cancer: a mendelian randomization study. Front Immunol. 2024;15:1444222. https://doi.org/10.3389/fimmu.2024.1444222.CrossRefPubMedPubMedCentral

30.

Chai W, Zhang M, He Y, Chai W. Characteristics of immune cells and causal relationship with chondromalacia: a two-sample, bidirectional mendelian randomization study. Mol Pain. 2024;20:17448069241289962. https://doi.org/10.1177/17448069241289962.CrossRefPubMedPubMedCentral

31.

Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74. https://doi.org/10.1038/nature15393.CrossRefPubMed

32.

Cai J, He L, Wang H, Rong X, Chen M, Shen Q, et al. Genetic liability for prescription opioid use and risk of cardiovascular diseases: a multivariable mendelian randomization study. Addiction (Abingdon England). 2022;117(5):1382–91. https://doi.org/10.1111/add.15767.CrossRefPubMed

33.

Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, et al. PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations. Bioinf (Oxford England). 2019;35(22):4851–3. https://doi.org/10.1093/bioinformatics/btz469.CrossRef

34.

Shi X, Wang T, Teng D, Hou S, Lin N. A mendelian randomization study investigates the causal relationship between immune cell phenotypes and cerebral aneurysm. Front Genet. 2024;15:1333855. https://doi.org/10.3389/fgene.2024.1333855.CrossRefPubMedPubMedCentral

35.

Brion MJ, Shakhbazov K, Visscher PM. Calculating statistical power in mendelian randomization studies. Int J Epidemiol. 2013;42(5):1497–501. https://doi.org/10.1093/ije/dyt179.CrossRefPubMed

36.

Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for mendelian randomization. Stat Methods Med Res. 2017;26(5):2333–55. https://doi.org/10.1177/0962280215597579.CrossRefPubMed

37.

Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46(6):1985–98. https://doi.org/10.1093/ije/dyx102.CrossRefPubMedPubMedCentral

38.

Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in mendelian randomization with some Invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304–14. https://doi.org/10.1002/gepi.21965.CrossRefPubMedPubMedCentral

39.

Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25. https://doi.org/10.1093/ije/dyv080.CrossRefPubMedPubMedCentral

40.

Li Y, Lai S, Kan X. Causal relationship between immune cells and telomere length: mendelian randomization analysis. BMC Immunol. 2024;25(1):19. https://doi.org/10.1186/s12865-024-00610-6.CrossRefPubMedPubMedCentral

41.

Pierce BL, Ahsan H, Vanderweele TJ. Power and instrument strength requirements for mendelian randomization studies using multiple genetic variants. Int J Epidemiol. 2011;40(3):740–52. https://doi.org/10.1093/ije/dyq151.CrossRefPubMed

42.

Burgess S, Thompson SG. Interpreting findings from mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32(5):377–89. https://doi.org/10.1007/s10654-017-0255-x.CrossRefPubMedPubMedCentral

43.

Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693–8. https://doi.org/10.1038/s41588-018-0099-7.CrossRefPubMedPubMedCentral

44.

Abbasi-Kenarsari H, Shafaghat F, Baradaran B, Movassaghpour AA, Shanehbandi D, Kazemi T. Cloning and expression of CD19, a human B-Cell marker in NIH-3T3 cell line. Avicenna J Med Biotechnol. 2015;7(1):39–44.PubMedPubMedCentral

45.

Susa KJ, Rawson S, Kruse AC, Blacklow SC. Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81. Science (New York, NY). 2021; 371, (6526):300–305. https://doi.org/10.1126/science.abd9836

46.

Zhang X, Jing J. Effect of peripheral blood lymphocytes on prognosis of multiple cancers. Cancer Control: J Moffitt Cancer Cent. 2023;30:10732748231202921. https://doi.org/10.1177/10732748231202921.CrossRef

47.

Sanz I, Wei C, Jenks SA, Cashman KS, Tipton C, Woodruff MC, et al. Challenges and opportunities for consistent classification of human B cell and plasma cell populations. Front Immunol. 2019;10:2458. https://doi.org/10.3389/fimmu.2019.02458.CrossRefPubMedPubMedCentral

48.

Saudi A, Banday V, Zirakzadeh AA, Selinger M, Forsberg J, Holmbom M, et al. Immune-activated B cells are Dominant in prostate Cancer. Cancers. 2023;15(3). https://doi.org/10.3390/cancers15030920.

49.

Kläsener K, Jellusova J, Andrieux G, Salzer U, Böhler C, Steiner SN, et al. CD20 as a gatekeeper of the resting state of human B cells. Proc Natl Acad Sci USA. 2021;118(7). https://doi.org/10.1073/pnas.2021342118.

50.

Shi JY, Gao Q, Wang ZC, Zhou J, Wang XY, Min ZH, et al. Margin-infiltrating CD20(+) B cells display an atypical memory phenotype and correlate with favorable prognosis in hepatocellular carcinoma. Clin cancer Research: Official J Am Association Cancer Res. 2013;19(21):5994–6005. https://doi.org/10.1158/1078-0432.ccr-12-3497.CrossRef

51.

Chee SJ, Lopez M, Mellows T, Gankande S, Moutasim KA, Harris S, et al. Evaluating the effect of immune cells on the outcome of patients with mesothelioma. Br J Cancer. 2017;117(9):1341–8. https://doi.org/10.1038/bjc.2017.269.CrossRefPubMedPubMedCentral

52.

Chung MKY, Gong L, Kwong DL, Lee VH, Lee AW, Guan XY, et al. Functions of double-negative B cells in autoimmune diseases, infections, and cancers. EMBO Mol Med. 2023;15(9):e17341. https://doi.org/10.15252/emmm.202217341.CrossRefPubMedPubMedCentral

53.

Li Y, Li Z, Hu F. Double-negative (DN) B cells: an under-recognized effector memory B cell subset in autoimmunity. Clin Exp Immunol. 2021;205(2):119–27. https://doi.org/10.1111/cei.13615.CrossRefPubMedPubMedCentral

54.

Centuori SM, Gomes CJ, Kim SS, Putnam CW, Larsen BT, Garland LL, et al. Double-negative (CD27(-)IgD(-)) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations. J Translational Med. 2018;16(1):30. https://doi.org/10.1186/s12967-018-1404-z.CrossRef

55.

Gong L, Kwong DL, Dai W, Wu P, Li S, Yan Q, et al. Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma. Nat Commun. 2021;12(1):1540. https://doi.org/10.1038/s41467-021-21795-z.CrossRefPubMedPubMedCentral

56.

Shukla A, Chen C, Jellusova J, Leung CR, Kao E, Bhat N, et al. Self-reactive B cells in the GALT are actively curtailed to prevent gut inflammation. JCI Insight. 2019;5(16). https://doi.org/10.1172/jci.insight.130621.

57.

Fang C, Li T, Li Y, Xu GJ, Deng QW, Chen YJ, et al. CD38 produces nicotinic acid adenosine dinucleotide phosphate in the lysosome. J Biol Chem. 2018;293(21):8151–60. https://doi.org/10.1074/jbc.RA118.002113.CrossRefPubMedPubMedCentral

58.

Wo YJ, Gan ASP, Lim X, Tay ISY, Lim S, Lim JC. The roles of CD38 and CD157 in the solid Tumor Microenvironment and Cancer Immunotherapy. Cells. 2019;9(1). https://doi.org/10.3390/cells9010026.

59.

Lohr M, Edlund K, Botling J, Hammad S, Hellwig B, Othman A, et al. The prognostic relevance of tumour-infiltrating plasma cells and immunoglobulin kappa C indicates an important role of the humoral immune response in non-small cell lung cancer. Cancer Lett. 2013;333(2):222–8. https://doi.org/10.1016/j.canlet.2013.01.036.CrossRefPubMed

Title: Association of B cells and the risk of Esophageal cancer: a bidirectional two-sample mendelian randomization study
Authors: Jinzhou Guo
Gao Si
Xuejie Song
Fuchun Si
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-024-13166-w

CSPG4P12 polymorphism served as a susceptibility marker for esophageal cancer in Chinese population

Open Access
Esophageal Cancer
Original Research

A multicenter high-quality data registry for advanced proton therapy approaches: the POWER registry

Open Access
Study Protocol

Identification of the cytoplasmic DNA-Sensing cGAS-STING pathway-mediated gene signatures and molecular subtypes in prostate cancer

Open Access
Prostate Cancer
Original Research

Efficacy and safety of add-on mirogabalin to conventional therapy for the treatment of peripheral neuropathic pain after thoracic surgery: the multicenter, randomized, open-label ADMIT-NeP study

Open Access
Neuropathic Pain
Original Research

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC)

Open Access
Hepatocellular Carcinoma
Study Protocol

Patient experiences: a qualitative systematic review of chemotherapy adherence

Open Access
Cytostatic Therapy
Review

Keynote series | Spotlight on menopause

Springer Medicine

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

Unlock free access to practice-relevant journal articles

Looking for something specific?

About journals on Springer Medicine

Abstract

Background and objectives

Methods

Results

Conclusions

Please log in to get access to this content