Non-invasive detection of biliary tract cancer by low-coverage whole genome sequencing from plasma cell-free DNA: A prospective cohort study

Wang, Xiang; Fu, Xiaohui; Zhou, Qian; Zhao, Teng; Duan, Anqi; Ruan, Xiang; Zhu, Bin; Li, Yin; Zhang, Yongjie; Yu, Wenlong

doi:10.1016/j.tranon.2020.100908

Cited by 8 publications

(4 citation statements)

References 55 publications

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“…Since GBCs harbor enriched copy number variations (CNVs) 14 , we inferred large-scale chromosomal CNVs from the RNA expression profiles to distinguish malignant EPCs (mEPCs) from non-malignant EPCs (nEPCs). Based on the initial cell-type identification, all the EPCs were extracted and inferred for CNVs in each cell, with endothelial cells as the reference and spike-in.…”

Section: Resultsmentioning

confidence: 99%

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma

et al. 2022

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Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with the lowest survival rate, primarily arising from chronic inflammation. To better characterize the progression from inflammation to cancer to metastasis, we performed single-cell RNA sequencing across samples of 6 chronic cholecystitis, 12 treatment-naive GBCs, and 6 matched metastases. Benign epithelial cells from inflamed gallbladders displayed resting, immune-regulating, and gastrointestinal metaplastic phenotypes. A small amount of PLA2G2A+ epithelial cells with copy number variation were identified from a histologically benign sample. We validated significant overexpression of PLA2G2A across in situ GBCs, together with increased proliferation and cancer stemness in PLA2G2A-overexpressing GBC cells, indicating an important role for PLA2G2A during early carcinogenesis. Malignant epithelial cells displayed pervasive cancer hallmarks and cellular plasticity, differentiating into metaplastic, inflammatory, and mesenchymal subtypes with distinct transcriptomic, genomic, and prognostic patterns. Chronic cholecystitis led to an adapted microenvironment characterized by MDSC-like macrophages, CD8+ TRM cells, and CCL2+ immunity-regulating fibroblasts. By contrast, GBC instigated an aggressive and immunosuppressive microenvironment, featured by tumor-associated macrophages, Treg cells, CD8+ TEX cells, and STMN1+ tumor-promoting fibroblasts. Single-cell and bulk RNA-seq profiles consistently showed a more suppressive immune milieu for GBCs with inflammatory epithelial signatures, coupled with strengthened epithelial-immune crosstalk. We further pinpointed a subset of senescence-like fibroblasts (FN1+TGM2+) preferentially enriched in metastatic lesions, which promoted GBC migration and invasion via their secretory phenotype. Collectively, this study provides comprehensive insights into epithelial and microenvironmental reprogramming throughout cholecystitis-propelled carcinogenesis and metastasis, laying a new foundation for the precision therapy of GBC.

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Section: Resultsmentioning

confidence: 99%

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma

et al. 2022

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“…Wang et al [ 31 ] collected plasma samples from 47 patients suspected of having lesions in the biliary tract. They utilized UCAD to analyze free DNA for CNV analysis through low-coverage whole genome sequencing.…”

Section: Ucad Application Prospectsmentioning

confidence: 99%

Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Qian,

Xie,

Zhao

et al. 2024

World J Gastrointest Surg

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Gastric cancer (GC) is a prevalent malignant tumor within the digestive system, with over 40% of new cases and deaths related to GC globally occurring in China. Despite advancements in treatment modalities, such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents, the prognosis for GC remains poor. New targeted therapies and immunotherapies are currently under investigation, but no significant breakthroughs have been achieved. Studies have indicated that GC is a heterogeneous disease, encompassing multiple subtypes with distinct biological characteristics and roles. Consequently, personalized treatment based on clinical features, pathologic typing, and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer (PLGC). Current research has categorized GC into four subtypes: Epstein-Barr virus-positive, microsatellite instability, genome stability, and chromosome instability (CIN). Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas. Among these, ultrasensitive chromosomal aneuploidy detection (UCAD) can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology, in conjunction with bioinformatics analysis, to achieve qualitative and quantitative detection of chromosomal stability. This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

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“…3 It is also possible that the low plasma detection rate may be due to the larger proportion with less than stage III disease compared to the studies done in patients with advanced BTC. 1,2,7 Because studies done with dedicated gene panels have higher rates of oncogenic mutations and low-coverage whole genome sequencing for the detection of aneuploidy reported higher plasma ctDNA detection, 9 the sequencing method used must also be considered.…”

Section: Promise Of Bile Circulating Tumor Dna In Biliary Tract Cancersmentioning

confidence: 99%

Promise of bile circulating tumor DNA in biliary tract cancers

Kearney

Weighill

Yeh

2023

Cancer

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An explosion of technological advances has facilitated the unprecedented use of liquid biopsy methods to isolate and interrogate circulating tumor DNA for precision oncology approaches. Liquid biopsy samples are not isolated to plasma but include bodily fluids such as urine and bile. In this issue, Ohyama et al. present a prospective study of patients with biliary tract cancers who underwent cell‐free DNA (cfDNA) isolation from bile and plasma, further demonstrating the feasibility and promise of bile cfDNA for biliary tract malignancies.

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Non-invasive detection of biliary tract cancer by low-coverage whole genome sequencing from plasma cell-free DNA: A prospective cohort study

Cited by 8 publications

References 55 publications

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma

Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Promise of bile circulating tumor DNA in biliary tract cancers

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