Pan-Cancer Analysis of Atrial-Fibrillation-Related Innate Immunity Gene ANXA4

Yan, Tao; Zhu, Shijie; Shi, Yu; Xie, Changming; Zhu, Miao; Zhang, Yangyang; Wang, Chunsheng; Guo, Changfa

doi:10.3389/fcvm.2021.713983

Cited by 9 publications

(5 citation statements)

References 44 publications

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“…Recent studies have identified ANXA4 gene as a hub immune‐related gene in AF, with significantly higher levels of ANXA4 expression in patients with AF than in normal subjects. 53 This may be related to the fact that ANXA4 affects the cardiac action potential or influences the contractility of the left atrium. 54 , 55 RAB1A is a member of the Ras superfamily of guanosine triphosphatases.…”

Section: Discussionmentioning

confidence: 99%

Proteome‐Wide Mendelian Randomization Analysis Identified Potential Drug Targets for Atrial Fibrillation

Wang,

Huang,

Jia

2023

JAHA

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Background Finding effective and safe therapeutic drugs for atrial fibrillation (AF) is an important concern for clinicians. Proteome‐wide Mendelian randomization analysis provides new ideas for finding potential drug targets. Methods and Results Using a proteome‐wide Mendelian randomization approach, we assessed the genetic predictive causality between thousands of proteins and AF risk and found that genetically predicted plasma levels of phosphomevalonate kinase, tumor necrosis factor ligand superfamily member 12, sulfhydryl oxidase 2, interleukin‐6 receptor subunit alpha, and low‐affinity immunoglobulin gamma Fc region receptor II‐b might decrease AF risk, while genetically predicted plasma levels of beta‐mannosidase, collagen alpha‐1(XV) chain, ANXA4 (annexin A4), COF2 (cofilin‐2), and RAB1A (Ras‐related protein Rab‐1A) might increase AF risk ( P <3.4×10 −5 ). By using different Mendelian randomization methods and instrumental variable selection thresholds, we performed sensitivity analyses in 30 scenarios to test the robustness of positive findings. Replication analyses were also performed in independent samples to further avoid false‐positive findings. Drugs targeting tumor necrosis factor ligand superfamily member 12, interleukin‐6 receptor subunit alpha, low‐affinity immunoglobulin gamma Fc region receptor II‐b, and annexin A4 are approved or in development. The results of the phenome‐wide Mendelian randomization analysis showed that changing the plasma levels of phosphomevalonate kinase, cofilin‐2, annexin A4, Ras‐related protein Rab‐1A, sulfhydryl oxidase 2, and collagen alpha‐1(XV) chain did not increase the risk of other diseases while decreasing the risk of AF. Conclusions We found a significant causal association between genetically predicted levels of 10 plasma proteins and AF risk. Four of these proteins have drugs targeting them that are approved or in development, and our results suggest the potential for these drugs to treat AF or cause AF. Sulfhydryl oxidase 2, low‐affinity immunoglobulin gamma Fc region receptor II‐b, and beta‐mannosidase have not been suggested by previous laboratory or epidemiological studies to be associated with AF and may reveal new pathophysiological pathways as well as therapeutic targets for AF.

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Section: Discussionmentioning

confidence: 99%

Proteome‐Wide Mendelian Randomization Analysis Identified Potential Drug Targets for Atrial Fibrillation

Wang,

Huang,

Jia

2023

JAHA

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“…TIMPs could control MMP that could lead to the degradation of the extracellular matrix and, consequently, organize the path for malignant cells to progress and spread to distant secondary areas ( 47 ). Third, certain immune-related genes identified in AF have recently been linked to the prognosis and immune infiltration in several tumor types ( 48 ). Herein, present KEGG and GO enrichment analyses of 51 common DEGs also revealed that these genes were significantly enriched in antioxidant activity, xenobiotic catabolic processes, and cytochrome P450 metabolism pathways.…”

Section: Discussionmentioning

confidence: 99%

Impact of genetically predicted atrial fibrillation on cancer risks: A large cardio-oncology Mendelian randomization study using UK biobank

Huang

Wang

et al. 2023

Front. Cardiovasc. Med.

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BackgroundIncreasing incidences of both atrial fibrillation (AF) and cancer have been observed in recent years. However, the casual association of both serious conditions has been scarcely evaluated and is considered to be a blank slate in cardio-oncology. Thus, we introduced Mendelian randomization (MR) methods to estimate the effects of AF on cancer risks.MethodsWe performed univariable and multivariable two-sample MR analyses to evaluate the effects of AF on the risk of 19 site-specific types of cancer. This MR study was conducted based on 111 independent AF-associated genetic instruments from genome-wide association studies and summarized-level data from corresponding cancer consortia. Multiple sensitivity analyses, including the leave-one-out analysis, MR-Egger regression, and MR-PRESSO tests, were further performed to examine the potential directional pleiotropic effects. Functional annotation was performed for common differentially expressed genes of AF and prostate cancer (PCA).ResultsA total of 6,777,155 European-descent people, including 533,725 cases and 6,243,430 controls, were included in the present MR analysis. Univariable MR analyses demonstrated a causal effect of AF on the incidence of PCA [odds ratio (OR): 0.96; 95% confidence interval (CI) 0.92–0.99, p = 0.01], and the causal effect remained significant (OR: 0.65; 95% CI 0.47–0.90, p = 0.01) after adjusting for potential confounders through the multivariable MR approach. However, no casual associations between AF and the other 18 site-specific cancer risks were observed (all p-values were > 0.05). The consistency of outcomes across complementary sensitivity MR methods further supported the causality. The functional analysis emphasized the essential role of antioxidant and xenobiotic catabolic processes in AF and PCA.ConclusionContrary to the findings of several previous observational studies, our comprehensive MR analyses did not corroborate a causal role for AF in increasing the risk of various types of cancer. They did, however, demonstrate that AF may decrease the risk of PCA. Studies from larger sample sizes and individuals with different ethnic backgrounds are required to further support our conclusions.

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“…Some studies have suggested that ANXA4 could play a role in modulating immune cell function and potentially impact tumor immune response. [ 31 ] VSIG4 encodes a transmembrane protein that regulates macrophage function. Recent research indicates that VSIG4 might be involved in modulating tumor immune response by regulating immune cell activity.…”

Section: Discussionmentioning

confidence: 99%

Construction of an aging-related risk signature in high-grade serous ovarian cancer for predicting survival outcome and immunogenicity

Liu,

et al. 2023

Medicine

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Studies have shown that aging significantly impacts tumorigenesis, survival outcome, and treatment efficacy in various tumors, covering high-grade serous ovarian cancer (HGSOC). Therefore, the objective for this investigation is to construct an aging-relevant risk signature for the first time, which will help evaluate the immunogenicity and survival status for patients with HGSOC. Totaling 1727 patients with HGSOC, along with their mRNA genomic data and clinical survival data, were obtained based on 5 independent cohorts. The Lasso-Cox regression model was utilized to identify the aging genes that had the most significant impact on prognosis. The risk signature was developed by integrating the determined gene expression and accordant model weights. Additionally, immunocytes in the microenvironment, signaling pathways, and immune-relevant signatures were assessed based on distinct risk subgroups. Finally, 2 cohorts that underwent treatment with immune checkpoint inhibitor (ICI) were employed to confirm the effects of identified risk signature on ICI efficacy. An aging signature was constructed from 12 relevant genes, which showed improved survival outcomes in low-risk HGSOC patients across discovery and 4 validation cohorts (all P < .05). The low-risk subgroup showed better immunocyte infiltration and higher enrichment of immune pathways and ICI predictors based on further immunology analysis. Notably, in the immunotherapeutic cohorts, low-risk aging signature was observed to link to better immunotherapeutic outcomes and increased response rates. Together, our constructed signature of aging has the potential to assess not only the prognosis outcome and immunogenicity, but also, importantly, the efficacy of ICI treatment. This signature provides valuable insights for prognosis prediction and immunotherapeutic effect evaluation, ultimately promoting individualized treatment for HGSOC patients.

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Pan-Cancer Analysis of Atrial-Fibrillation-Related Innate Immunity Gene ANXA4

Cited by 9 publications

References 44 publications

Proteome‐Wide Mendelian Randomization Analysis Identified Potential Drug Targets for Atrial Fibrillation

Proteome‐Wide Mendelian Randomization Analysis Identified Potential Drug Targets for Atrial Fibrillation

Impact of genetically predicted atrial fibrillation on cancer risks: A large cardio-oncology Mendelian randomization study using UK biobank

Construction of an aging-related risk signature in high-grade serous ovarian cancer for predicting survival outcome and immunogenicity

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