Whole blood microRNAs capture systemic reprogramming and have diagnostic potential in patients with biliary tract cancer

Høgdall, Dan; O’Rourke, Colm J.; Larsen, Finn Ole; Zarforoushan, Shahryar; Christensen, Trine; Ghazal, Awaisa; Boisen, Mogens K.; Munoz‐Garrido, Patricia; Johansen, Julia S.; Andersen, Jesper B.

doi:10.1016/j.jhep.2022.05.036

Cited by 15 publications

(4 citation statements)

References 36 publications

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“…In order to obtain biomarkers with high specificity and abundant diversity to GC, the different types of miRNA and mRNA were selected to screen biomarkers, and their serum expression levels in a sequencing cohort were analyzed by the NGS method (Table S1). − The differential gene expression volcano maps based on the sequencing results are plotted in Figure A and B. With FC ≥ 2, p < 0.05, and CPM or FPKM > 0 as the criteria, five mRNAs (XKR9, G0S2, ACAT2, SLC25A17, and PLS3) and three miRNAs (miR-5585-3p, miR-5585-5p, and miR-658) were selected as candidates preliminarily.…”

Section: Results and Discussionmentioning

confidence: 99%

The Dual-Response–Single-Amplification Fluorescent Nanomachine for Tumor Imaging and Gastric Cancer Diagnosis

Zhang,

Tong,

Huang

et al. 2023

ACS Nano

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Gastric cancer (GC) is one of the most common tumors worldwide and is the leading cause of tumor-related mortality. Traditional biomarkers and screening methods cannot meet the clinical demands. There is an urgent need for highly sensitive diagnostic markers as well as accurate quantification methods for early gastric cancer (EGC) screening. Here a dual-target cooperatively responsive fluorescent nanomachine by the innovative application of two targets� responsive strand migration system with a single-amplificationcycle element was developed for the simultaneous detection of GC biomarkers miR-5585-5p and PLS3 mRNA, which were selected by next-generation sequencing and RT-qPCR. It was also an RNA extraction-free, PCR-free, and nonenzymatic biosensor to achieve tumor cell imaging and serum diagnosis. Requiring only a 20 μL serum sample and 20 min incubation time, the nanomachine achieved an ultrasensitive detection limit of fM level with a broad linear range from fM to nM. More importantly, a higher AUC value (0.884) compared to the clinically used biomarker CA 72-4 was obtained by the nanomachine to distinguish GC patients successfully. Notably, for the key concerns of diagnosis of EGC patients, the nanomachine also achieved a satisfactory AUC value of 0.859. Taken together, this work has screened and obtained multiple biomarkers and developed a fluorescent nanomachine for combination diagnosis of GC, providing an ingenious design of a functionalized DNA nanomachine and a feasible strategy for the transformation of serum biomarkers into clinical diagnosis.

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Section: Results and Discussionmentioning

confidence: 99%

The Dual-Response–Single-Amplification Fluorescent Nanomachine for Tumor Imaging and Gastric Cancer Diagnosis

Zhang,

Tong,

Huang

et al. 2023

ACS Nano

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“…In the present study, miRNA-Seq and RT-qPCR analyses indicated that miR-92b-5p was more highly enriched in salivary exosomes from individuals with lung cancer (Figure 3). Previous studies suggested that miR-92b-5p could be used for predicting the prognosis of gastric cancer (Xu et al, 2021) and biliary tract cancer (Høgdall et al, 2022), suggesting that this exosomal miRNA might have the potential to be used as a diagnostic biomarker of lung cancer. Although other studies have also associated miR-532-3p with cancer (Han et al, 2019;Jiang et al, 2019), salivary exosomal miR-532-3p deserves further investigation.…”

Section: Discussionmentioning

confidence: 99%

Comparative analyses of salivary exosomal miRNAs for patients with or without lung cancer

Liu,

Yu,

et al. 2023

Front. Genet.

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Introduction: Lung cancer is the most frequent cause of cancer-related deaths worldwide. Exosomes are involved in different types of cancer, including lung cancer.Methods: We collected saliva from patients with (LC) or without (NC) lung cancer and successfully isolated salivary exosomes by ultracentrifugation. MiRNA sequencing was implemented for the exosome samples from NC and LC groups, dgeR was used to determine differentially expressed miRNAs (DE miRNAs), and quantitative real-time polymerase chain reaction (qPCR) was used to verify three differentially expressed microRNAs (miRNAs).Results: A total of 372 miRNAs were identified based on the sequencing results. Subsequently, 15 DE miRNAs were identified in LC vs. NC, including eight upregulated miRNAs and seven downregulated miRNAs. Some DE miRNAs were validated via qPCR. A total of 488 putative target genes of the upregulated DE miRNAs were found, and the functional analyses indicated that numerous target genes were enriched in the pathways associated with cancer.Discussion: This suggests that miRNAs of salivary exosomes might have the potential to be used as biomarkers for prediction and diagnosis of lung cancer.

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“…Considering inflammatory reactions and biomarkers may precede cancer diagnosis by years, and the immunosuppressive microenvironment resulting from chronic inflammation can contribute to the development and activation of cancer. Over the past decade, various miRNA-based signatures have been developed to diagnose certain cancer types [ 5 – 9 ], however, the limited sample size and incomplete model construction methods hinders their clinical utility. Also, few study focused on the diagnostic performance of immune-related miRNAs.…”

Section: Main Textmentioning

confidence: 99%

Pan-cancer characterization of cell-free immune-related miRNA identified as a robust biomarker for cancer diagnosis

Wu,

Zhang,

Tang

et al. 2024

Mol Cancer

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Minimally invasive testing is essential for early cancer detection, impacting patient survival rates significantly. Our study aimed to establish a pioneering cell-free immune-related miRNAs (cf-IRmiRNAs) signature for early cancer detection. We analyzed circulating miRNA profiles from 15,832 participants, including individuals with 13 types of cancer and control. The data was randomly divided into training, validation, and test sets (7:2:1), with an additional external test set of 684 participants. In the discovery phase, we identified 100 differentially expressed cf-IRmiRNAs between the malignant and non-malignant, retaining 39 using the least absolute shrinkage and selection operator (LASSO) method. Five machine learning algorithms were adopted to construct cf-IRmiRNAs signature, and the diagnostic classifies based on XGBoost algorithm showed the excellent performance for cancer detection in the validation set (AUC: 0.984, CI: 0.980–0.989), determined through 5-fold cross-validation and grid search. Further evaluation in the test and external test sets confirmed the reliability and efficacy of the classifier (AUC: 0.980 to 1.000). The classifier successfully detected early-stage cancers, particularly lung, prostate, and gastric cancers. It also distinguished between benign and malignant tumors. This study represents the largest and most comprehensive pan-cancer analysis on cf-IRmiRNAs, offering a promising non-invasive diagnostic biomarker for early cancer detection and potential impact on clinical practice.

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Whole blood microRNAs capture systemic reprogramming and have diagnostic potential in patients with biliary tract cancer

Cited by 15 publications

References 36 publications

The Dual-Response–Single-Amplification Fluorescent Nanomachine for Tumor Imaging and Gastric Cancer Diagnosis

The Dual-Response–Single-Amplification Fluorescent Nanomachine for Tumor Imaging and Gastric Cancer Diagnosis

Comparative analyses of salivary exosomal miRNAs for patients with or without lung cancer

Pan-cancer characterization of cell-free immune-related miRNA identified as a robust biomarker for cancer diagnosis

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