Dataset Information

Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study.

ABSTRACT:

Background

Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship.

Methods

For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-way two-sample Mendelian randomization (MR) analysis was carried out in this study. The aim was to determine whether specific immune cell traits have a causal impact on the risk of RCC. In order to achieve this, publicly accessible genetic data was utilized to examine and establish the potential relationship between 731 immune cell characteristics and the likelihood of developing RCC. Additionally, various techniques were applied to verify the reliability, variability, and presence of horizontal pleiotropy in the outcomes.

Results

We found a bidirectional causal relationship between RCC and immune cells according to the MR analysis results. It should be noted that CD4-CD8-T cells (OR = 1.61, 95%CI = 1.02-2.55, P = 4.07 × 10^-2) pose a risk for RCC, whereas BAFF-R (OR = 0.69, 95%CI = 0.53-0.89, P = 5.74 × 10^-3) and CD19 (OR = 0.59, 95%CI = 1.02-2.55, P = 4.07 × 10^-2) on B cells act as protective factors. Furthermore, the presence of RCC reduces the levels of B cells (OR = 1.05, 95%CI = 1.01-1.09, P = 1.19 × 10^-2) and CD8 + T cells (OR = 1.04, 95%CI = 1.00-1.08, P = 2.83 × 10^-2).

Conclusions

Our research illustrates the intricate correlation between immune cells and RCC, presenting novel insights for the prospective safeguarding against RCC risk and the exploration of fresh therapeutic targets.

SUBMITTER: Lu Z

PROVIDER: S-EPMC11005164 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study.

Lu Zhongwen Z Yin Yu Y Rao Tian T Xu Xinchi X Zhao Kai K Liu Zhanpeng Z Qin Chao C Tang Min M

BMC cancer 20240409 1

<h4>Background</h4>Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship.<h4>Methods</h4>For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-w ...[more]

PMID: 38594655

Similar Datasets

Project description:BackgroundComplex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings.MethodsComprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results.ResultsAfter FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P-values, including FSC-A on NKT (β = 0.119, 95% CI = 0.044 ~ 0.194, P = 0.002), DN (CD4-CD8-) NKT %T cell (β = 0.131, 95% CI = 0.054 ~ 0.208, P = 9.03 × 10- 4), and SSC-A on lymphocytes (β = 0.136, 95% CI = 0.059 ~ 0.213, P = 5.43 × 10- 4). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI = 0.051 ~ 0.203, P = 1.09 × 10- 3). SCZ also had a causal effect on IgD+ %B cell (β = 0.130, 95% CI = 0.054 ~ 0.207, P = 8.69 × 10- 4), and DP (CD4+CD8+) %T cell (β = 0.131, 95% CI = 0.054 ~ 0.207, P = 8.05 × 10- 4). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4+ %T cell (OR = 0.986, 95% CI = 0.979 ~ 0.992, P = 1.37 × 10- 5), HLA DR on CD14- CD16- (OR = 0.738 (95% CI = 0.642 ~ 0.849, P = 2.00 × 10- 5), CD33dim HLA DR+ CD11b- AC (OR = 0.631, 95% CI = 0.529 ~ 0.753, P = 3.40 × 10- 7) and activated & resting Treg % CD4 Treg (OR = 0.937, 95% CI = 0.906 ~ 0.970, P = 1.96 × 10- 4).ConclusionsOur study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.

Project description:Lung cancer (LC) is the leading cause of cancer-related deaths in China, with its incidence and mortality rates rising annually. Various studies have demonstrated disparities in immune cell counts and profiles between LC patients and healthy individuals. However, the existence of a causal link remains largely uncertain. To explore the potential causal association between immune cells and LC risk, a Mendelian randomization (MR) approach was employed. Employing immune cell genome-wide association study (GWAS) data from a public database (n = 731 subjects) and Lung Cancer Genome Research Consortium's GWAS dataset (n = 492,803 participants), unconventional genetic loci remarkably associated with the significant abundance of 731 types of immune cells were extracted according to preset threshold points as instrumental variables. The primarily analytical strategy involved the inverse variance weighting (IVW) method, with the effect size estimates expressed as odds ratio (OR) and 95% CI. The robustness of the findings was assessed through a leave-one-out sensitivity analysis, heterogeneity test, horizontal gene pleiotropy test, MR-PRESSO and MR-Egger. The MR analysis identified a significant association between 18 distinct immune cell types and lung cancer risk. MR analysis revealed that 7 types of immune cells, including CD20 on IgD - CD38 - B cell, CD20 on switched memory B cell, IgD on IgD + CD24 + B cell, BAFF - R on IgD - CD38 + B cell, CD39 + resting CD4 regulatory T cell Absolute Count, CD127 on CD45RA + CD4 + T cell, CD8 on Effector Memory CD8 + T cell, displayed a protective effect against lung cancer development. Conversely, 11 other immune cells populations were positive associated with an increased lung cancer risk. In contrast, reverse MR analysis indicated that the lung cancer risk was linked to 11 immune cells, with 2 types of immune cells (CD25 on IgD - CD27 - B cell, CD4 + T cell %leukocyte) showing a are positive correlation with cancer development, whereas 9 types of immune cells appeared to be inversely regulated. These findings collectively imply that specific immune cell populations may play critical roles in either promoting or suppressing the initiation and progression of lung cancer. The findings of this study offer fresh insights into the underlying biological mechanisms governing lung cancer development, thereby opening new avenues for future research in the domain of LC. The identification of specific immune cell subsets with protective or promoting roles provides crucial leads for preventive and therapeutic strategies. These insights have the potential to enhance early detection methods and inform the development of more effective treatment approaches, ultimately benefiting patient outcomes and improving the overall management of lung cancer.

Project description:BackgroundUveitis, characterized by inflammation of the iris, ciliary body, and choroid, presents a significant global clinical challenge, contributing substantially to visual impairment. Risk factors include autoimmune diseases and immune cell dysfunctions, yet many remain unidentified. Immune cells, notably T cells, B cells, and monocytes, play pivotal roles in uveitis pathogenesis. While biologic agents show promise, comprehensive studies on immune cell types in ocular diseases are lacking. Genome-wide association studies (GWAS) and Mendelian randomization (MR) present promising avenues to elucidate genetic susceptibilities and causal relationships between immune cell traits and uveitis risk.MethodsTwo-sample MR analysis was used to evaluate the causal relationship between 731 immune cells and uveitis, and genome-wide significance analysis was performed for genetic variation in 731 immune cells traits (P < 5 × 10-8). Immune characteristics include median fluorescence intensity (MFI), relative cell counts (RC), absolute cell counts (AC), and morphological parameters (MP), which were determined by published GWAS, and public data from the IEU Open GWAS database. The main analysis method of MR is inverse variance weighting (IVW). Heterogeneity and horizontal pleiotropy were also assessed.Results5 immunophenotypes, including CD62L-DC %DC, IgD+ CD38dim %B cell, CD3 on CM CD4+T cell, CD3 on CD45RA-CD4 +T cell, and CD3 on CD39+ CD4+ Treg may increase the risk of uveitis. 5 immunophenotypes, including CD11b on CD33dim HLA DR-Myeloid cell, HLA DR on CD33dim HLA DR+ CD11b-myeloid cell, CD14-CD16 + %monocyte, HLA DR on CD14-CD16 + monocyte and PDL-1 on CD14-CD16 + monocyte was negatively associated with the risk of uveitis. Among them, HLA DR on CD14-CD16 + monocyte (OR=0.921, 95%CI =0.875-0.970, P=0.001) and HLA DR on CD33dim HLA DR+ CD11b- (OR=0.879, 95%CI = 0.833-0.927, P=0.00) were negatively associated with the risk of uveitis in bi-direction.ConclusionThese results indicate that 10 immune cells traits are significantly associated with the risk of developing uveitis and 2 of them were strongly associated with uveitis bi-directionally, after excluding the effects of confounding factors such as some immune diseases, which provided new ideas and therapeutic targets for the study of immune mechanism of uveitis.

Project description:BackgroundThere is still limited research on the association between immune cells and the risk of prostate cancer. Further investigations are warranted to comprehend the intricate associations at play.MethodsWe used a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between immune cell phenotypes and prostate cancer. The summary data for immune cell phenotypes was derived from a study cohort, including 3,757 individuals from Sardinia with data on 731 immune cell phenotypes. The summary data for prostate cancer were obtained from the UK Biobank database. Sensitivity analyses were conducted, and the combination of MR-Egger and MR-Presso was used to assess horizontal pleiotropy. Cochran's Q test was employed to evaluate heterogeneity, and the results were subjected to FDR correction.ResultsOur study identified two immune cell phenotypes significantly associated with the risk of prostate cancer, namely CD25 on naive-mature B cells (OR = 0.998, 95% CI, 0.997-0.999, P = 2.33E-05, FDR = 0.017) and HLA DR on CD14- CD16- cells (OR = 1.001, 95% CI, 1.000-1.002, P = 8.01E-05, FDR = 0.03). When adjusting FDR to 0.2, we additionally found six immune cell phenotypes influencing the incidence of prostate cancer. These include FSC-A on B cells (OR = 1.002, 95% CI, 1.001-1.002, P = 7.77E-04, FDR = 0.133), HLA DR on plasmacytoid dendritic cells (OR = 1.001, 95% CI, 1.000-1.001, P = 0.001, FDR = 0.133), CD14+ CD16- monocyte % monocytes (OR = 1.002, 95% CI, 1.001-1.003, P = 0.001, FDR = 0.133), and HVEM on effector memory CD4+ T cells (OR = 1.001, 95% CI, 1.000-1.002, P = 0.002, FDR = 0.169), which are positively correlated with the risk of prostate cancer. Conversely, CD25 on IgD+ B cells (OR = 0.998, 95% CI, 0.997-0.999, P = 0.002, FDR = 0.169) and Monocytic Myeloid-Derived Suppressor Cells AC (OR = 0.999, 95% CI, 0.999-1.000, P = 0.002, FDR = 0.17) are negatively correlated with the risk of prostate cancer.ConclusionThis study has revealed causal relationships between immune cell phenotypes and prostate cancer, supplying novel insights that might aid in identifying potential therapeutic targets of prostate cancer.

Dataset Information

Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study.

Background

Methods

Results

Conclusions

Publications

Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets