scholarly journals Bacteria-Derived Extracellular Vesicles in Urine as a Novel Biomarker for Gastric Cancer: Integration of Liquid Biopsy and Metagenome Analysis

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4687
Author(s):  
Jae-Yong Park ◽  
Chil-Sung Kang ◽  
Ho-Chan Seo ◽  
Jin-Chul Shin ◽  
Sung-Min Kym ◽  
...  

Early detection is crucial for improving the prognosis of gastric cancer, but there are no non-invasive markers for the early diagnosis of gastric cancer in real clinical settings. Recently, bacteria-derived extracellular vesicles (EVs) emerged as new biomarker resources. We aimed to evaluate the microbial composition in gastric cancer using bacteria-derived EVs and to build a diagnostic prediction model for gastric cancer with the metagenome data. Stool, urine, and serum samples were prospectively collected from 453 subjects (gastric cancer, 181; control, 272). EV portions were extracted from the samples for metagenome analysis. Differences in microbial diversity and composition were analyzed with 16S rRNA gene profiling, using the next-generation sequencing method. Biomarkers were selected using logistic regression models based on relative abundances at the genus level. The microbial composition of healthy groups and gastric cancer patient groups was significantly different in all sample types. The compositional differences of various bacteria, based on relative abundances, were identified at the genus level. Among the diagnostic prediction models for gastric cancer, the urine-based model showed the highest performance when compared to that of stool or serum. We suggest that bacteria-derived EVs in urine can be used as novel metagenomic markers for the non-invasive diagnosis of gastric cancer by integrating the liquid biopsy method and metagenome analysis.

Lab on a Chip ◽  
2018 ◽  
Vol 18 (24) ◽  
pp. 3790-3801 ◽  
Author(s):  
Peng Zhang ◽  
Jennifer Crow ◽  
Divya Lella ◽  
Xin Zhou ◽  
Glenson Samuel ◽  
...  

A microwell-patterned microfluidic digital mRNA analysis platform enables PCR-free, single-molecule detection of EWS-FLI1 fusion transcripts in EVs towards liquid biopsy-based non-invasive diagnosis of Ewing Sarcoma.


2019 ◽  
Vol 20 (5) ◽  
pp. 1114 ◽  
Author(s):  
Germana Rappa ◽  
Caterina Puglisi ◽  
Mark Santos ◽  
Stefano Forte ◽  
Lorenzo Memeo ◽  
...  

The diagnostic approach to thyroid cancer is one of the most challenging issues in oncology of the endocrine system because of its high incidence (3.8% of all new cancer cases in the US) and the difficulty to distinguish benign from malignant non-functional thyroid nodules and establish the cervical lymph node involvement during staging. Routine diagnosis of thyroid nodules usually relies on a fine-needle aspirate biopsy, which is invasive and often inaccurate. Therefore, there is an urgent need to identify novel, accurate, and non-invasive diagnostic procedures. Liquid biopsy, as a non-invasive approach for the detection of diagnostic biomarkers for early tumor diagnosis, prognosis, and disease monitoring, may be of particular benefit in this context. Extracellular vesicles (EVs) are a consistent source of tumor-derived RNA due to their prevalence in circulating bodily fluids, the well-established isolation protocols, and the fact that RNA in phospholipid bilayer-enclosed vesicles is protected from blood-borne RNases. Recent results in other types of cancer, including our recent study on plasma EVs from glioblastoma patients suggest that information derived from analysis of EVs from peripheral blood plasma can be integrated in the routine diagnostic tumor approach. In this review, we will examine the diagnostic and prognostic potential of liquid biopsy to detect tumor-derived nucleic acids in circulating EVs from patients with thyroid carcinoma.


Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 219
Author(s):  
Jae Ri Kim ◽  
Kyulhee Han ◽  
Youngmin Han ◽  
Nayeon Kang ◽  
Tae-Seop Shin ◽  
...  

Novel biomarkers for early diagnosis of pancreatic cancer (PC) are necessary to improve prognosis. We aimed to discover candidate biomarkers by identifying compositional differences of microbiome between patients with PC (n = 38) and healthy controls (n = 52), using microbial extracellular vesicles (EVs) acquired from blood samples. Composition analysis was performed using 16S rRNA gene analysis and bacteria-derived EVs. Statistically significant differences in microbial compositions were used to construct PC prediction models after propensity score matching analysis to reduce other possible biases. Between-group differences in microbial compositions were identified at the phylum and genus levels. At the phylum level, three species (Verrucomicrobia, Deferribacteres, and Bacteroidetes) were more abundant and one species (Actinobacteria) was less abundant in PC patients. At the genus level, four species (Stenotrophomonas, Sphingomonas, Propionibacterium, and Corynebacterium) were less abundant and six species (Ruminococcaceae UCG-014, Lachnospiraceae NK4A136 group, Akkermansia, Turicibacter, Ruminiclostridium, and Lachnospiraceae UCG-001) were more abundant in PC patients. Using the best combination of these microbiome markers, we constructed a PC prediction model that yielded a high area under the receiver operating characteristic curve (0.966 and 1.000, at the phylum and genus level, respectively). These microbiome markers, which altered microbial compositions, are therefore candidate biomarkers for early diagnosis of PC.


Author(s):  
Dehua Liu ◽  
Si Chen ◽  
Yawen Gou ◽  
Wenyong Yu ◽  
Hangcheng Zhou ◽  
...  

BackgroundGastric microbiota may be involved in gastric cancer. The relationship between gastrointestinal microbes and the risk of gastric cancer is unclear. This study aimed to explore the gastric and intestinal bacteria associated with gastritis and gastric precancerous lesions. We conducted a case-control study by performing 16S rRNA gene analysis of gastric biopsies, juices, and stool samples from 148 cases with gastritis or gastric precancerous lesions from Anhui and neighboring provinces, China. And we validated our findings in public datasets.ResultsAnalysis of microbial sequences revealed decreased bacterial alpha diversity in gastric bacteria during the progression of gastritis. Helicobacter pylori was the main contributor to the decreased microbial composition and diversity in the gastric mucosa and had little influence on the microbiota of gastric juice and feces. The gastric mucosal genera Gemella, Veillonella, Streptococcus, Actinobacillus, and Hemophilus had the higher degree of centrality across the progression of gastric precancerous lesions. And Acinetobacter may contribute to the occurrence of intraepithelial neoplasia. In addition, the microbial model of H. pylori-positive gastric biopsies and feces showed value in the prediction of gastric precancerous lesions.ConclusionsThis study identified associations between gastric precancerous lesions and gastric microbiota, as well as the changes in intestinal microbiota, and explored their values in the prediction of gastric precancerous lesions.


2021 ◽  
Vol 22 (14) ◽  
pp. 7707
Author(s):  
Chiara Romano ◽  
Federica Martorana ◽  
Maria Stella Pennisi ◽  
Stefania Stella ◽  
Michele Massimino ◽  
...  

Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient’s diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 489-489
Author(s):  
Dong Ho Lee ◽  
Mijin Seol ◽  
Yu Ra Lee ◽  
Young Soo Park ◽  
Cheol Min Shin ◽  
...  

489 Background: Dysbiosis of intestinal microbiota is promoting the development of colorectal cancer (CRC). We confirmed the intestinal microbiota composition from fecal sample of Korean CRC patients. Metagenomic analysis was performed and we isolated single microbes through culture-based method. Methods: CRC fecal samples were collected from 12 individuals. Metagenome Sequencing was based on the 16S rRNA gene amplicon on the Illumina MiSeq platform. The bacteria strains were subcultivated on the agar plate medium in aerobic and anaerobic and further identified by using the 16s rRNA gene sequencing. Results: Bacteria diversity by metagenome analysis was decreased in CRC group compared to control group. In CRC group, relative abundance of Firmicutes and Bacteroidetes were increased while the prevalence of Proteobacteria was decreased. The difference of microbial composition between control and CRC group was found at the genus level. Bacteroides, Parabacteroides of Bacteroidetes have increased and Acinetobacter, Pseudomonas of Proteobacteria have significantly decreased in CRC compared to control group. Using culture method, we isolated diverse bacteria of species level including five strains of Bacteroides; B. ovatus, B. uniformis, B. salyersiae, B. vulgatus and B. xylanisolvens and two strains of Fusobacterium; F. gonidiaformans and F. necrophorum from CRC patients. Conclusions: Metagenome analysis showed the genus Bacteroides, Parabacteroides of the phylum Bacteroidetes has increased and the genus Acinetobacter, Pseudomonas of Proteobacteria decreased in CRC group compared to control group. In addition to, we have isolated various strains associated with CRC by culture-based method.


Author(s):  
Xinmei Zhang ◽  
Chao Li ◽  
Weijun Cao ◽  
Zhenyu Zhang

ObjectiveMicrobial infections have been shown to contribute to gastric carcinogenesis, the knowledge of gastric microbiota alteration in this process may provide help in early diagnosis of gastric cancer. The aim of this study was to characterize the microbial changes and identify taxonomic biomarkers across stages of gastric carcinogenesis.MethodsThe gastric microbiota was investigated by 16S rRNA gene analysis in gastric mucosal specimens from 47 patients including superficial gastritis (SG), atrophic gastritis (AG), gastric intraepithelial neoplasia (GIN), and gastric cancer (GC). Differences in microbial composition across the disease stages, especially in GIN and GC were assessed using linear discriminant analysis effect size.ResultsThere was no gradual changing trend in the richness or diversity of the gastric microbiota across stages of gastric carcinogenesis. The relative abundance of dominant taxa at phylum and genus levels didn’t show a gradual shift pattern, and the only four taxa that continuously enriched from SG to GC were Slackia, Selenomonas, Bergeyella, and Capnocytophaga, all of which were oral bacteria. The most representative taxa which were enriched in GC patients were oral bacteria including Parvimonas, Eikenella and Prevotella-2, and environmental bacteria including Kroppenstedtia, Lentibacillus, and Oceanobacillus. The gastric microbiota in GIN patients were characterized by enrichment of intestinal commensals including Romboutsia, Fusicatenibacter, Prevotellaceae-Ga6A1-group, and Intestinimonas. Gastric cardia cancer and non-cardia cancer patients had significantly different microbiota profiles characterized by a higher abundance of Helicobacter in the cardia cancer patients.ConclusionsOur results provide insights on potential taxonomic biomarkers for gastric cancer and precancerous stages, and suggest that gastric microbiota might play different roles in the carcinogenesis of cardia cancer and non-cardia cancer.


Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.


Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 254
Author(s):  
Ying Wang ◽  
Jianqing Zhu ◽  
Jie Fang ◽  
Li Shen ◽  
Shuojia Ma ◽  
...  

We characterized the gut microbial composition and relative abundance of gut bacteria in the larvae and adults of Pieris canidia by 16S rRNA gene sequencing. The gut microbiota structure was similar across the life stages and sexes. The comparative functional analysis on P. canidia bacterial communities with PICRUSt showed the enrichment of several pathways including those for energy metabolism, immune system, digestive system, xenobiotics biodegradation, transport, cell growth and death. The parameters often used as a proxy of insect fitness (development time, pupation rate, emergence rate, adult survival rate and weight of 5th instars larvae) showed a significant difference between treatment group and untreated group and point to potential fitness advantages with the gut microbiomes in P. canidia. These data provide an overall view of the bacterial community across the life stages and sexes in P. canidia.


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