A Series of Genes for Predicting Responses to Anti-Tumor Necrosis Factor α Therapy in Crohn’s Disease

Nie, Kai; Zhang, Chao; Deng, Minzi; Luo, Weiwei; Ma, Kejia; Wu, Xing; Yang, Yuanyuan; Wang, Xiaoyan

doi:10.3389/fphar.2022.870796

Cited by 4 publications

(4 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors showed that the basic gene responsible for the lack of reaction to anti-TNF α is the TLR2 gene. Higher expression of this gene in patients’ monocytes resulted in a higher inflammation and worse response to treatment [76]. It is worth noting that transcriptomic analysis in both CD patient’s tissue and in vitro cell culture treated with an anti-TNF agent also provides information on potential pharmacogenetic biomarkers, for example, as in the case of recent studies by Kwak et al .…”

Section: Omics Research In Anti-tnf Pharmacogeneticsmentioning

confidence: 99%

Apoptosis and inflammatory genes variants in primary non-response to anti-TNF therapy in Crohn’s disease patients

Łykowska‐Szuber

Walczak

Dobrowolska

et al. 2023

European Journal of Gastroenterology &Amp; Hepatology

View full text Add to dashboard Cite

Anti-TNF therapy has indeed revolutionized the treatment of Crohn’s disease, leading to higher rates of response and remission in patients. However, a significant proportion of 20–40% of patients do not respond to the initial therapy, others experience a secondary loss of response with ongoing treatment. Adverse drug reactions also occur in some patients. The effectiveness of anti-TNF treatment may be influenced by genetic variability, including FCGR3A, ADAM17, TNFRSF1A, TNFRSF1B, FAS, FASL, IL1B, CASP9, and MIF genes. In this article, we provide an overview of the current knowledge and findings in the pharmacogenetics of anti-TNF drugs in CD focusing on the aspect of apoptosis and inflammatory genes variants in primary non-response. Pharmacogenetic investigations have been conducted to identify genetic markers that can predict response to anti-TNF therapy. However, large multi-center validation studies and multi-loci algorithms development are required to effectively prognose the treatment effect. The identification of predictive markers of response to anti-TNF therapy can help clinicians make informed decisions about treatment options and minimize adverse drug reactions in patients.

show abstract

Section: Omics Research In Anti-tnf Pharmacogeneticsmentioning

confidence: 99%

Apoptosis and inflammatory genes variants in primary non-response to anti-TNF therapy in Crohn’s disease patients

Łykowska‐Szuber

Walczak

Dobrowolska

et al. 2023

European Journal of Gastroenterology &Amp; Hepatology

View full text Add to dashboard Cite

show abstract

“…Microarray technology is widely used to screen for genomic level differential alterations and can be used to participate in the prediction of CD development and progression. Nie et al identified TLR2, TREM1, CXCR1, FPR1, and FPR2 as promising candidates for predicting anti-TNFα responses in CD patients by microarray analysis ( Nie et al, 2022 ). Hu et al found that Hsa_circ_0062142 and hsa_circ_0001666 may play a key role in pathogenesis and serve as potential biomarkers of CD by microarray analysis ( Hu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Identifying hub genes and miRNAs in Crohn’s disease by bioinformatics analysis

Sun

Cai

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Introduction: Crohn’s disease (CD) is a disease that manifests mainly as chronic inflammation of the gastrointestinal tract, which is still not well understood in terms of its pathogenesis. The aim of this study was to use bioinformatics analysis to identify differentially expressed genes (DEGs) and miRNAs with diagnostic and therapeutic potential in CD.Materials and methods: Three CD datasets (GSE179285, GSE102133, GSE75214) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs between normal and CD tissues were identified using the GEO2R online tool. The Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were conducted using the clusterProfiler function in the R package. Protein-protein interaction network (PPI) analysis and visualization were performed with STRING and Cytoscape. Ten hub genes were identified using cytoHubba’s MCC algorithm and validated with datasets GSE6731 and GSE52746. Finally, the miRNA gene regulatory network was constructed by Cytoscape and NetworkAnalyst to predict potential microRNAs (miRNAs) associated with DEGs.Results: A total of 97 DEGs were identified, consisting of 88 downregulated genes and 9 upregulated genes. The enriched functions and pathways of the DEGs include immune system process, response to stress, response to cytokine and extracellular region. KEGG pathway analysis indicates that the genes were significantly enriched in Cytokine-cytokine receptor interaction, IL-17 signaling pathway, Rheumatoid arthritis and TNF signaling pathway. In combination with the results of the protein-protein interaction (PPI) network and CytoHubba, 10 hub genes including IL1B, CXCL8, CXCL10, CXCL1, CXCL2, CXCL5, ICAM1, IL1RN, TIMP1 and MMP3 were selected. Based on the DEG-miRNAs network construction, 5 miRNAs including hsa-mir-21-5p, hsa-mir-93-5p, hsa-mir-98-5p, hsa-mir-1-3p and hsa-mir-335-5p were identified as potential critical miRNAs.Conclusion: In conclusion, a total of 97 DEGs, 10 hub genes and 5 miRNAs that may be involved in the progression or occurrence of CD were identified in this study, which could be regarded as biomarkers of CD.

show abstract

“…In a recent study, TLR-2 was identified as one of the markers of a non-response pathway [31]. In another study, it was reported that infliximab decreased the expression of TLR-4 and TLR-5, the study indicated that higher TLR-4 and TLR-5 expression exacerbated inflammatory conditions in ankylosing spondylitis [36].…”

Section: Discussionmentioning

confidence: 96%

“…Infliximab alters the expression of adhesion molecules, pro-apoptotic genes, and transcription factors [29]. Additionally, some studies have shown that TLRs and MMPs contribute to non-response [30,31], the expression of Fig. 8 C. cassia aCE (A (L929) and B (U937)) was better at downregulating the expression of both Toll-like receptors than TCA (C (L929) and D (U937)), TCA downregulated the expression of TLR-4 more than TLR-2.…”

Section: Discussionmentioning

confidence: 99%

An in vitro study elucidating the synergistic effects of aqueous cinnamon extract and an anti-TNF-α biotherapeutic: implications for a complementary and alternative therapy for non-responders

Khedkar,

Khan

2024

BMC Complement Med Ther

View full text Add to dashboard Cite

Background Tumor necrosis factor-alpha (TNF-α) is a critical pro-inflammatory cytokine, and its abnormal production is associated with several immune mediated inflammatory diseases (IMID). Biological anti-TNF-α therapy includes treatment with monoclonal antibodies such as infliximab which have proven successful and are well-tolerated in most patients. Unfortunately, some patients may not respond to therapy (primary non-responders) or may lose sensitivity to the biological agent over time (early and late secondary non-responders). Natural products can reduce inflammation and act synergistically with small molecules or biologics, although evidence remains limited. This study aimed to investigate whether complementary and alternative medicine (CAM) could play a role in infliximab non-responders. Reportedly, cinnamon can help manage chronic inflammatory conditions owing to its anti-inflammatory properties. Methods We studied the synergistic effects of cinnamon and infliximab in vitro using a two-step approach. First, we investigated whether cinnamon and infliximab act synergistically. Second, we selected conditions that supported statistically significant synergy with infliximab and studied the mRNA expression of several genes involved in non-response to infliximab. We used aqueous cinnamon extract (aCE) from Cinnamomum cassia, Cinnamomum zeylanicum, and Cinnamomum loureiroi and bioactive trans-cinnamaldehyde (TCA), cinnamic acid (CA), and eugenol to study the synergy between infliximab and aCE/bioactive compounds using bioassays in fibroblast (L929) and monocytic (U937) cell lines, followed by qPCR for molecular-level insights. TCA, C. cassia aCE, and C. zeylanicum aCE demonstrated a dose-dependent synergistic effect with infliximab. Moreover, we saw differential gene expression for adhesion molecules, apoptotic factors, signaling molecules, and matrix remodelers in presence and absence of aCE/bioactives. Results CAM supplementation was most effective with C. cassia aCE, where a synergistic effect was observed for all the tested genes specifically for MMP-1, BcL-xL, Bax and JAK2, followed by TCA, which affected most of the tested genes except TLR-2, MMP1, MMP3, TIMP-1, and BAX, and C. zeylanicum aCE, which did not affect ICAM-1, VCAM-1, TLR-2, TLR-4, MMP1, MMP3, TIMP-1, and STAT3. Conclusion In conclusion, cinnamon acted synergistically with infliximab to mitigate inflammation when used as an extract. Purified bioactive TCA also showed synergistic activity. Thus, aCE, or cinnamon bioactive may be used as a CAM to improve patients’ quality of life.

show abstract

A Series of Genes for Predicting Responses to Anti-Tumor Necrosis Factor α Therapy in Crohn’s Disease

Cited by 4 publications

References 54 publications

Apoptosis and inflammatory genes variants in primary non-response to anti-TNF therapy in Crohn’s disease patients

Apoptosis and inflammatory genes variants in primary non-response to anti-TNF therapy in Crohn’s disease patients

Identifying hub genes and miRNAs in Crohn’s disease by bioinformatics analysis

An in vitro study elucidating the synergistic effects of aqueous cinnamon extract and an anti-TNF-α biotherapeutic: implications for a complementary and alternative therapy for non-responders

Contact Info

Product

Resources

About