scholarly journals Association between colorectal cancer and Fusobacterium nucleatum and Bacteroides fragilis bacteria in Iranian patients: a preliminary study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Normal Tissue ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Normal Mucosa ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Adjacent Normal Mucosa ◽  
Iranian Patients

Abstract Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.

scholarly journals The Clinicopathological Significance of miR-133a in Colorectal Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Timothy Ming-Hun Wan ◽  
Colin Siu-Chi Lam ◽  
Lui Ng ◽  
Ariel Ka-Man Chow ◽  
Sunny Kit-Man Wong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Negative Correlation ◽  
Target Genes ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Tnm Staging ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Endogenous Expression ◽  
Clinicopathological Significance

This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient’s clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson’s method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (γ=-), whereas CAV1 exhibited a significant positive correlation (γ=), and a stronger correlation was found in patients who developed distant metastases (γ=). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis.

scholarly journals DNA methylation markers for diagnosis and prognosis of common cancers

2017 ◽  
Vol 114 (28) ◽  
pp. 7414-7419 ◽  
Author(s):  
Xiaoke Hao ◽  
Huiyan Luo ◽  
Michal Krawczyk ◽  
Wei Wei ◽  
Wenqiu Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cancer Biology ◽  
Normal Tissue ◽  
Diagnostic Methods ◽  
Adjacent Normal Tissue ◽  
Tissue Samples ◽  
Diagnosis And Prognosis ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis.

scholarly journals Elevated miRNA Inversely Correlates with E-cadherin Gene Expression in Tissue Biopsies from Crohn Disease Patients in contrast to Ulcerative Colitis Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Małgorzata Guz ◽  
Tomasz Dworzański ◽  
Witold Jeleniewicz ◽  
Marek Cybulski ◽  
Joanna Kozicka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn Disease ◽  
Normal Tissue ◽  
Normal Mucosa ◽  
Normal Colonic Mucosa ◽  
Adjacent Normal Tissue ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
E Cadherin

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn disease (CD). Similar symptoms, but different treatment procedures for both diseases require precise diagnosis. MicroRNAs (miRNAs) are major posttranscriptional players that regulate the expression of genes during the inflammation and thus could be appropriate biomarkers for differentiation between UC and CD. For this purpose, we analyzed the expression of miR-21-3p, miR-31-3p, miR-125b-1-3p, miR-146a-3p, miR-155-5p, and E-cadherin (CDH1) genes associated with IBD, in 67 tissue samples: 28 inflamed mucosa samples (n=16 UC, n=12 CD), 28 adjacent normal colonic mucosa (n=16 UC, n=12 CD), and 11 normal mucosa from healthy patients using reverse transcription real-time RT-PCR. We found all analyzed miRNAs were significantly overexpressed in UC tissue as compared to adjacent normal tissue of patients with UC, as well as to normal mucosa from healthy controls. Four miRNAs (except miR-125b-1-3p) were significantly upregulated in CD lesions as compared to adjacent normal tissue of patients with CD, and four miRNAs, except miR-146a-3p, were significantly higher in CD samples compared to normal mucosa from healthy individuals. In the CD group, we found an inverse correlation between miR-155-5p or miR-146a-3p expressions and CDH1expression in inflamed mucosa. This type of correlation was also detected for miR-213p in adjacent normal tissue and CDH1 in inflamed mucosa, as well as between miR-155-5p and CDH1 in adjacent normal tissue. Elevated miRNA expression is characteristic for IBD-mediated inflammation process and inversely correlated with CDH1 gene expression, which suggest involvement of epithelial to mesenchymal transition (EMT) in IBD development.

scholarly journals 16S rRNA of Mucosal Colon Microbiome and CCL2 Circulating Levels Are Potential Biomarkers in Colorectal Cancer

2021 ◽  
Vol 22 (19) ◽  
pp. 10747
Author(s):  
Carmela Nardelli ◽  
Ilaria Granata ◽  
Marcella Nunziato ◽  
Mario Setaro ◽  
Fortunata Carbone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
16S Rrna ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Normal Weight ◽  
Western World ◽  
Intestinal Dysbiosis ◽  
Rrna Sequencing ◽  
Circulating Levels

Colorectal cancer (CRC) is one of the most common malignancies in the Western world and intestinal dysbiosis might contribute to its pathogenesis. The mucosal colon microbiome and C-C motif chemokine 2 (CCL2) were investigated in 20 healthy controls (HC) and 20 CRC patients using 16S rRNA sequencing and immunoluminescent assay, respectively. A total of 10 HC subjects were classified as overweight/obese (OW/OB_HC) and 10 subjects were normal weight (NW_HC); 15 CRC patients were classified as OW/OB_CRC and 5 patients were NW_CRC. Results: Fusobacterium nucleatum and Escherichia coli were more abundant in OW/OB_HC than in NW_HC microbiomes. Globally, Streptococcus intermedius, Gemella haemolysans, Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were significantly increased in CRC patient tumor/lesioned tissue (CRC_LT) and CRC patient unlesioned tissue (CRC_ULT) microbiomes compared to HC microbiomes. CCL2 circulating levels were associated with tumor presence and with the abundance of Fusobacterium nucleatum, Bacteroides fragilis and Gemella haemolysans. Our data suggest that mucosal colon dysbiosis might contribute to CRC pathogenesis by inducing inflammation. Notably, Fusobacterium nucleatum, which was more abundant in the OW/OB_HC than in the NW_HC microbiomes, might represent a putative link between obesity and increased CRC risk.

scholarly journals Interaction Between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

2017 ◽  
Author(s):  
Ce Yuan ◽  
Michael Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Normal Tissue ◽  
Microbial Community Composition ◽  
Taxonomic Composition ◽  
Integrated Analysis ◽  
Tissue Samples ◽  
Microbiome Composition ◽  
Normal Tissues ◽  
Mirnas Expression

AbstractBackgroundAlthough variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNAs expression in human CRC tumor and normal tissues and the microbiome composition associated with these same tissues.MethodWe sequenced the small RNAs from patient-matched tumor and normal tissue samples collected from 44 human CRC patients performed an integrated analysis with microbiome taxonomic composition data from these same samples. We then interrogated the functions of the bacteria correlated with miRNAs that were differentially expressed (DE) between tumor and matched normal tissues, as well as the functions of miRNAs correlated with bacterial taxa that have been previously associated with CRC, including Fusobacterium, Providencia, Bacteroides, Akkermansia, Roseburia, Porphyromonas, and Peptostreptococcus.ResultsWe identified 76 miRNAs as DE between CRC and normal tissue, including known oncogenic miRNAs miR-182, miR-503, and miR-17∼92. These DE miRNAs were correlated with the relative abundance of several bacterial taxa, including Firmicutes, Bacteroidetes, and Proteobacteria. Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions, and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa.ConclusionsOur work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. Our results support a role for miRNAs in mediating a bi-directional host-microbiome interaction in CRC. In addition, we highlight sets of potentially interacting microbes and host miRNAs, suggesting several pathways that can be targeted via future therapies.

scholarly journals The Four Horsemen in Colon Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Marco Antonio Hernández-Luna ◽  
Sergio López-Briones ◽  
Rosendo Luria-Pérez
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Gastrointestinal Tract ◽  
Salmonella Enterica ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Cancer Development ◽  
Gastrointestinal Neoplasms ◽  
Intestinal Dysbiosis ◽  
Incidence And Mortality

Worldwide, neoplasms of the gastrointestinal tract have a very high incidence and mortality. Among these, colorectal cancer, which includes colon and rectum malignancies, representing both highest incidence and mortality. While gallbladder cancer, another neoplasm associated to gastrointestinal tract occurs less frequently. Genetic factors, inflammation and nutrition are important risk factors associated with colorectal cancer development. Likewise, pathogenic microorganisms inducing intestinal dysbiosis have become an important scope to determine the role of bacterial infection on tumorigenesis. Interestingly, in human biopsies of different types of gastrointestinal tract cancer, the presence of different bacterial strains, such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Salmonella enterica have been detected, and it has been considered as a high-risk factor to cancer development. Therefore, pathogens infection could contribute to neoplastic development through different mechanisms; including intestinal dysbiosis, inflammation, evasion of tumoral immune response and activation of pro-tumoral signaling pathways, such as β catenin. Here, we have reviewed the suggested bacterial molecular mechanisms and their possible role on development and progression of gastrointestinal neoplasms, focusing mainly on colon neoplasms, where the bacteria Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Salmonella enterica infect.

scholarly journals Detection of Fusobaterium nucleatum in feces and colorectal mucosa as a risk factor for colorectal cancer: a systematic review and meta-analysis

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Amal Idrissi Janati ◽  
Igor Karp ◽  
Claudie Laprise ◽  
Hisham Sabri ◽  
Elham Emami
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Systematic Reviews ◽  
Meta Analysis ◽  
Positive Association ◽  
Fusobacterium Nucleatum ◽  
Relevant Information ◽  
Colorectal Carcinogenesis ◽  
Qualitative Synthesis ◽  
Tissue Samples

Abstract Background Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Accumulating evidence suggests a potentially important role of colorectal infection with Fusobacterium nucleatum (F. nucleatum) in colorectal carcinogenesis. We conducted a systematic review, including both a qualitative synthesis and a meta-analysis, to synthesize the evidence from the epidemiological literature on the association between F. nucleatum detection in the colon/rectum and CRC. Methods A systematic literature search of Ovid MEDLINE(R), Embase, Web of Science Core Collection, EBM Reviews—Cochrane Database of Systematic Reviews, and CINAHL Plus with Full Text was conducted using earliest inclusive dates up to 4 October 2020. Eligible studies were original, comparative observational studies that reported results on colorectal F. nucleatum detection and CRC. Two independent reviewers extracted the relevant information. Odds ratio (OR) estimates were pooled across studies using the random effects model. Newcastle-Ottawa scale was used to critically appraise study quality. Results Twenty-four studies were included in the systematic review, of which 12 were included in the meta-analysis. Studies investigated F. nucleatum in feces, colorectal tissue samples, or both. In most studies included in the systematic review, the load of F. nucleatum was higher, on average, in specimens from CRC patients than in those from CRC-free controls. Meta-analysis showed a positive association between F. nucleatum detection in colorectal specimens and CRC (OR = 8.3; 95% confidence interval (95% CI) 5.2 to 13.0). Conclusions The results of this systematic review suggest that F. nucleatum in the colon/rectum is associated with CRC. Systematic review registration This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on July 10, 2018 (registration number CRD42018095866).

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