The causal relationship between gut microbiota and biliary tract cancer: comprehensive bidirectional Mendelian randomization analysis

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Март 15, 2024

Background Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore causal relationship between microbiota and BTC, conduct an appraisal of microbiome’s utility in facilitating early diagnosis BTC. Methods We acquired summary data for Genome-wide Association Studies (GWAS) pertaining BTC (418 cases 159,201 controls) from Biobank Japan (BBJ) database. Additionally, GWAS relevant (N = 18,340) were sourced MiBioGen consortium. The primary methodology employed analysis consisted Inverse Variance Weighting (IVW). Evaluations sensitivity carried out through utilization multiple statistical techniques, encompassing Cochrane’s Q test, MR-Egger intercept evaluation, global test MR-PRESSO, a leave-one-out methodological analysis. Ultimately, reverse Mendelian Randomization was conducted assess potential reciprocal causality. Results outcomes derived IVW substantiated presence Family Streptococcaceae (OR 0.44, P 0.034), Veillonellaceae 0.46, 0.018), Genus Dorea 0.29, 0.041) exerted protective influence against Conversely, Class Lentisphaeria 2.21, 0.017), Lachnospiraceae FCS020 Group 2.30, 0.013), Order Victivallales 0.017) adverse impact. To any effect, we used as exposure outcome, this revealed associations five different types microbiota. disclosed absence empirical indicators either heterogeneity or pleiotropy. Conclusion investigation represents inaugural identification indicative supporting beneficial detrimental relationships risk determined MR methodologies. These could hold significance formulation individualized therapeutic strategies at prevention survival enhancement.

Язык: Английский

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N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Апрель 20, 2024

Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality poor prognosis. Important function invests circRNAs tremendous potential in biomarkers therapeutic targets. Nevertheless, it is still unknown how contribute evolution ICC. CircRNAs paired ICC adjacent tissues were screened by sequencing. To explore impact on development, experiments involving gain loss conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, pull-down, chromatin (ChIP), ubiquitination assays so employed identify molecular regulatory role circRNAs. Herein, we reported new circRNA, which originates from exon 9 15 SLCO1B3 gene (named circSLCO1B3), orchestrated progression promoting tumor proliferation, metastasis immune evasion. We found that circSLCO1B3 was highly overexpressed related lymphatic metastasis, sizes, differentiation. Mechanically, not only promoted proliferation via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity suppressing ubiquitin-proteasome-dependent degradation PD-L1 E3 ubiquitin ligase SPOP. further methyltransferase like 3 (METTL3) mediated m6A methylation stabilizes its expression. Our findings indicate prognostic marker target patients. Taken together, m6A-modified correlated prognosis enhancing potentiating HOXC8 expression, inducing evasion antagonizing degradation. These results suggest for

Язык: Английский

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Advancements in the application of ablative therapy and its combination with immunotherapy in anti-cancer therapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер 1880(2), С. 189285 - 189285

Опубликована: Фев. 10, 2025

Язык: Английский

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Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Фев. 23, 2024

Gastrointestinal (GI) tumors are a significant global health threat, with high rates of morbidity and mortality. Exosomes contain various biologically active molecules like nucleic acids, proteins, lipids can serve as messengers for intercellular communication. They play critical roles in the exchange information between tumor cells microenvironment (TME). The TME consists mesenchymal components extracellular matrix (ECM), fibroblasts being most abundant cell type mesenchyme. Cancer-associated (CAFs) derived from normal stem that activated TME. CAFs secrete exosomes to modulate proliferation, invasion, migration, drug resistance, other biological processes tumors. Additionally, manipulate function behavior through direct cell-cell interactions. This review provides summary crosstalk GI exosomes, along potential underlying mechanisms.

Язык: Английский

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Unravelling immune microenvironment features underlying tumor progression in the single-cell era

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Апрель 22, 2024

Abstract The relationship between the immune cell and tumor occurrence progression remains unclear. Profiling alterations in microenvironment (TIME) at high resolution is crucial to identify factors influencing cancer enhance effectiveness of immunotherapy. However, traditional sequencing methods, including bulk RNA sequencing, exhibit varying degrees masking cellular heterogeneity immunophenotypic changes observed early late-stage tumors. Single-cell (scRNA-seq) has provided significant precise TIME landscapes. Consequently, this review highlighted molecular tumorigenesis elucidated through recent scRNA-seq studies. Specifically, we have summarized different stages, early, late, metastatic stages. Moreover, outlined related variations that may promote metastasis single-cell era. widespread applications will comprehensively redefine understanding biology furnish more effective immunotherapy strategies.

Язык: Английский

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Syngeneic murine models with distinct immune microenvironments represent subsets of human intrahepatic cholangiocarcinoma

Journal of Hepatology, Год журнала: 2024, Номер 80(6), С. 892 - 903

Опубликована: Март 7, 2024

•Transposase-mediated transduction of Fbxw7ΔF and Akt into the biliary epithelium promotes CCA carcinogenesis.•Murine cells derived from Fbxw7ΔF/Akt tumors can be implanted orthotopically mouse livers to generate a syngeneic model (FAC).•This recapitulates critical phenotypic pathological elements human iCCA.•Syngeneic murine models with different genetic drivers correspond subsets CCA.•Syngeneic iCCA display genotype-immune microenvironment phenotype correlation differential responses immunotherapy. Background & AimsCholangiocarcinoma (CCA) is poorly immunogenic malignancy associated limited survival. Syngeneic immunocompetent are an essential tool elucidate tumor immune (TIME), understand mechanisms evasion, test novel immunotherapeutic strategies. The scope this study was develop characterize distinct drivers, correlate genomics, immunobiology, therapeutic response.MethodsA multifaceted approach including scRNA-seq, CITE-seq, whole exome bulk RNA sequencing employed. FDA-approved PD-1/PD-L1 antibodies were tested in humanized mice (HuPD-H1).ResultsA intrahepatic (iCCA) driven by intrabiliary that mimics generated. From tumors, cell line (FAC) characteristics developed. Established SB1 (YAPS127A/Akt) KPPC (KrasG12Dp53L/L) compared FAC model. Although had transcriptomic similarities, they substantial differences as well. Mutation patterns FAC, SB1, matched mutational signatures Western Japanese patient cohorts. high mutation burden. T cell-infiltrated TIME, while preponderance suppressive myeloid cells. Moreover, tumor-bearing HuPD-H1 displayed nivolumab or durvalumab.ConclusionsSyngeneic between genotype TIME phenotype, immunotherapies. This underscores importance leveraging multiple preclinical immunotherapy CCA.Impact implicationsUnderstanding relationship unmet need cholangiocarcinoma (CCA). Herein, we use demonstrate models, which information will help guide other studies. Additionally, it emphasizes checkpoint inhibition patients not "one-size-fits-all" approach. Our observations suggest that, for targeted therapies, should stratified selected treatment according their genetics. Cholangiocarcinoma response. A (HuPD-H1). durvalumab. CCA.

Язык: Английский

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Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma

Cancers, Год журнала: 2024, Номер 16(8), С. 1537 - 1537

Опубликована: Апрель 17, 2024

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA molecularly heterogeneous and exhibits broad spectrum of histopathological features. It highly aggressive carcinoma with high mortality poor survival rates. ICCAs are classified into two main subtypes: small-duct type large-duct types. These tumor types have different cell origins clinicopathological numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, EGFR, FGFR2 fusion. Two subtypes—inflammation proliferation—have been proposed. Recent advances high-throughput assays using next-generation sequencing improved our understanding pathogenesis genetics. The diagnosis poses significant challenge for pathologists because its varied morphologies phenotypes. Accurate essential effective patient management prognostic determination. This article provides an updated overview pathology, focusing particularly on features, histological subtypes, diagnostic approaches.

Язык: Английский

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Targeting tumorous Circ-E-Cadherinencoded C-E-Cad inhibits the recruitment and function of breast cancer-associated myeloid-derived suppressor cells

Pharmacological Research, Год журнала: 2024, Номер 204, С. 107204 - 107204

Опубликована: Май 2, 2024

We previously demonstrated that the C-E-cad protein encoded by circ-E-cadherin promotes self-renewal of glioma stem cells. The expression pattern in breast cancer and its potential function tumor microenvironment are unclear. was detected specimens. influence on MDSCs assessed using FACS vivo tumorigenesis experiments. synergistic effect anti-C-E-cad anti-PD-1 antibodies validated vivo. were found to be upregulated vs. normal samples. recruitment MDSCs, especially PMN-MDSCs. activates EGFR signaling cells transcription CXCL8; moreover, binds maintains glycolysis Targeting enhanced efficiency. Our data suggested is markedly overexpressed MDSC survival. increases efficacy immune checkpoint inhibitor therapy.

Язык: Английский

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Interdependence of macrophages and T-cells in partial spontaneous regression of intrahepatic cholangiocarcinoma in a cow: a histopathologic perspective

Comparative Clinical Pathology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Язык: Английский

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Role of genomics in liver transplantation for cholangiocarcinoma

Current Opinion in Organ Transplantation, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Purpose of review The purpose this is to summarize the current knowledge cholangiocarcinoma molecular biology and suggest a framework for implementation next-generation sequencing in all stages liver transplantation. This timely as recent guidelines recommend increased use these technologies with promising results. Recent findings main themes covered here address germline somatic genetic alterations recently discovered cholangiocarcinoma, particularly those associated prognosis treatment responses, nascent efforts translate into contemporary practice peri-liver transplantation period. Summary Early profiling care demonstrate growing number potentially actionable alterations. Still lacking consensus on what biomarkers adopt, at scale cost, how integrate them most effectively ambition increasing patients eligible improving their long-term outcomes.

Язык: Английский

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