scholarly journals Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer

Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 654-662 ◽  
Author(s):  
Olabisi Oluwabukola Coker ◽  
Geicho Nakatsu ◽  
Rudin Zhenwei Dai ◽  
William Ka Kei Wu ◽  
Sunny Hei Wong ◽  
...  

ObjectivesBacteriome and virome alterations are associated with colorectal cancer (CRC). Nevertheless, the gut fungal microbiota in CRC remains largely unexplored. We aimed to characterise enteric mycobiome in CRC.DesignFaecal shotgun metagenomic sequences of 184 patients with CRC, 197 patients with adenoma and 204 control subjects from Hong Kong were analysed (discovery cohort: 73 patients with CRC and 92 control subjects; validation cohort: 111 patients with CRC, 197 patients with adenoma and 112 controls from Hong Kong). CRC-associated fungal markers and ecological changes were also validated in additional independent cohorts of 90 patients with CRC, 42 patients with adenoma and 66 control subjects of published repository sequences from Germany and France. Assignment of taxonomies was performed by exact k-mer alignment against an integrated microbial reference genome database.ResultsPrincipal component analysis revealed separate clusters for CRC and control (p<0.0001), with distinct mycobiomes in early-stage and late-stage CRC (p=0.0048). Basidiomycota:Ascomycota ratio was higher in CRC (p=0.0042), with increase in Malasseziomycetes (p<0.0001) and decrease in Saccharomycetes (p<0.0001) and Pneumocystidomycetes (p=0.0017). Abundances of 14 fungal biomarkers distinguished CRC from controls with an area under the receiver-operating characteristic curve (AUC) of 0.93 and validated AUCs of 0.82 and 0.74 in independent Chinese cohort V1 and European cohort V2, respectively. Further ecological analysis revealed higher numbers of co-occurring fungal intrakingdom and co-exclusive bacterial–fungal correlations in CRC (p<0.0001). Moreover, co-occurrence interactions between fungi and bacteria, mostly contributed by fungal Ascomycota and bacterial Proteobacteria in control, were reverted to co-exclusive interplay in CRC (p=0.00045).ConclusionsThis study revealed CRC-associated mycobiome dysbiosis characterised by altered fungal composition and ecology, signifying that the gut mycobiome might play a role in CRC.

2016 ◽  
Vol 15 (6) ◽  
pp. 772-779 ◽  
Author(s):  
Leping Li ◽  
Ying Guo ◽  
Yuezhi Chen ◽  
Jinshen Wang ◽  
Lei Zhen ◽  
...  

Background: Colorectal cancer is one of the most common cancers worldwide in terms of both incidence and mortality. The associations of expressions of tissue and plasma miR-29b were not detected in this study. Methods: There are 400 healthy age- and gender-matched controls enrolled in this study in a rate of 1:2. The receiver operating characteristic curve analysis was undertaken using the expression level for miR-29b in the colorectal cancer specimens from patients with cancer and healthy controls to assess the diagnostic accuracy of both tissue and plasma miR-29b levels. Results: It was found that the expression of plasma miR-29b is associated with the tissue miR-29b. Advanced study showed that aberrant miR-29b expression in both cancer tissues and plasma is associated with the clinicopathological data of patients with colorectal cancer. Tissue miR-29b showed an AUC of 0.883, with a sensitivity of 81.6% and a specificity of 84.9%. However, the AUC for plasma miR-29b was 0.743, with a sensitivity of 61.4% and a specificity of 72.5%. The analyses of the biological effects of miR-29b for colorectal cancer showed that miR-29b could inhibit the cell viability and migration. Conclusion: In summary, our data suggest that both the tissue and the plasma miR-29b levels have some value as a diagnostic tool for colorectal cancer. Advanced biological effects were conducted to detect the potential effect on the cell viability and migration. Future investigations including larger patient populations and patients with early-stage colorectal cancer are needed to confirm the potential diagnostic value of miRNA-29b in colorectal cancer.


2007 ◽  
Vol 25 (19) ◽  
pp. 2696-2701 ◽  
Author(s):  
Zhenwen Zhao ◽  
Yijin Xiao ◽  
Paul Elson ◽  
Haiyan Tan ◽  
Sarah J. Plummer ◽  
...  

Purpose Plasma levels of lysophospholipids were evaluated as potential biomarkers for colorectal cancer (CRC), where a highly reliable and minimally invasive blood test is lacking. Patients and Methods Patients with CRC (n = 133) and control subjects (n = 125) were recruited through the Cleveland Clinic. Preoperative plasma samples were analyzed for lysophospholipid levels using liquid chromatography mass spectrometry in a blinded fashion. Participants were randomly divided in a 2:1 ratio into a “training set” (TS) and a “validation set” (VS). Logistic regression models were used in the TS to identify markers that best discriminated between CRC and controls. A cutoff point for the final discriminating model was developed using the receiver operating characteristic curve to achieve 95% specificity. All analyses were then independently validated in the VS. Results Plasma levels of several lysophosphatidylcholines (LPCs), including 18:1- and 18:2-LPC, were significantly decreased in CRC patients compared with controls (P < .001). A model based on total saturated LPC and the difference between the proportional amounts of 18:2-LPC and 18:1-LPC in the unsaturated LPC fraction was derived from the TS. This model achieved a sensitivity and specificity of 82% and 93%, respectively, in the VS. Overall, 118 (94%) of 125 control subjects and 113 (85%) of 133 CRC cases were correctly identified, including eight (89%) of nine CRC cases with stage T1 disease. Conclusion Percentage of 18:1-LPC or 18:2-LPC plasma levels compared with total saturated LPC levels, either individually or in combination, may represent potential biomarkers for CRC.


2018 ◽  
Vol 51 (6) ◽  
pp. 2704-2715 ◽  
Author(s):  
Dongzhi Hu ◽  
Yang Zhan ◽  
Kegan Zhu ◽  
Ming Bai ◽  
Jiayi Han ◽  
...  

Background/Aims: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths worldwide. Thus, methods for early diagnosis of CRC are urgently needed. We aimed to identify potential long non-coding RNAs (lncRNAs) in circulatory exosomes that may serve as biomarkers for the detection of early-stage CRC. Methods: Exosomes from the plasma of CRC patients (n = 50) and healthy individuals (n = 50) were isolated by ultracentrifugation, followed by extraction of total exosomal RNAs using TRIzol reagent. Microarray analysis was used for exosomal lncRNA profiling in the two groups, and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression level of lncRNAs in all patients and healthy subjects. Results: The expression of six lncRNAs (LNCV6_116109, LNCV6_98390, LNCV6_38772, LNCV_108266, LNCV6_84003, and LNCV6_98602) was found to be significantly up-regulated in CRC patients compared with that in healthy individuals by qRT-PCR. The receiver operating characteristic curve was used to verify their diagnostic accuracy. The values of the area under the curve for these lncRNAs were 0.770 (LNCV6_116109), 0.7500 (LNCV6_98390), 0.6500 (LNCV6_38772), 0.6900 (LNCV_108266), 0.7500 (LNCV6_84003), and 0.7200 (LNCV6_98602). Conclusion: Our study suggested that the expression of these six exosomal lncRNAs (LNCV6_116109, LNCV6_98390, LNCV6_38772, LNCV_108266, LNCV6_84003, and LNCV6_98602) was significantly up-regulated in the plasma of CRC patients, and that they may serve as potential non-invasive biomarkers for early diagnosis of CRC.


2020 ◽  
pp. bjophthalmol-2019-315746
Author(s):  
Zhen Ji Chen ◽  
Li Ma ◽  
Marten E Brelen ◽  
Haoyu Chen ◽  
Motokazu Tsujikawa ◽  
...  

PurposeThe endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2 (tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis.MethodsThis study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2 were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed.ResultsTwo SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities.ConclusionThis study revealed TIE2 as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role.


2021 ◽  
Vol 11 ◽  
Author(s):  
Miao Yu ◽  
Xing-guo Song ◽  
Ya-jing Zhao ◽  
Xiao-han Dong ◽  
Li-min Niu ◽  
...  

BackgroundExosomes derived from cancer cells encapsulate various kinds of tumor-specific molecules and thus can interact with adjacent or distant cells to mediate information exchange. Long non-coding RNAs (lncRNAs) in exosomes have the potential as diagnostic and prognostic biomarkers in different types of cancers. The current study was aimed to identify circulating exosomal lncRNAs for the diagnosis of colorectal cancer (CRC).MethodsExosomes were isolated from the serum by ultracentrifugation and verified by transmission electron microscope (TEM), qNano, and immunoblotting. Exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 were selected by lncRNA microarray and validated by qPCR in 203 CRC patients and 201 healthy donors. The receiver operating characteristic curve (ROC) was used to assess the diagnostic efficiency of serum exosomal lncRNAs.ResultsExosomal FOXD2-AS1, NRIR, and XLOC_009459 (TCONS_00020073) levels were significantly upregulated in 203 CRC patients and 80 early-stage CRC patients compared to 201 healthy donors, possessing the area under the curve (AUC) of 0.728, 0.660, and 0.682 for CRC, as well as 0.743, 0.660, and 0.689 for early-stage CRC, respectively. Notably, their combination demonstrated the markedly elevated AUC of 0.736 for CRC and 0.758 for early-stage CRC, indicating their potential as diagnostic biomarkers for CRC.ConclusionsOur data suggested that exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 act as the promising biomarkers for the diagnostics of CRC and early-stage CRC.


2018 ◽  
Vol 29 ◽  
pp. viii33-viii34
Author(s):  
E. Letellier ◽  
M. Schmitz ◽  
A. Ginolhac ◽  
E. Koncina ◽  
M. Marchese ◽  
...  

Author(s):  
Shu-Farn Tey ◽  
Chung-Feng Liu ◽  
Tsair-Wei Chien ◽  
Chin-Wei Hsu ◽  
Kun-Chen Chan ◽  
...  

Unplanned patient readmission (UPRA) is frequent and costly in healthcare settings. No indicators during hospitalization have been suggested to clinicians as useful for identifying patients at high risk of UPRA. This study aimed to create a prediction model for the early detection of 14-day UPRA of patients with pneumonia. We downloaded the data of patients with pneumonia as the primary disease (e.g., ICD-10:J12*-J18*) at three hospitals in Taiwan from 2016 to 2018. A total of 21,892 cases (1208 (6%) for UPRA) were collected. Two models, namely, artificial neural network (ANN) and convolutional neural network (CNN), were compared using the training (n = 15,324; ≅70%) and test (n = 6568; ≅30%) sets to verify the model accuracy. An app was developed for the prediction and classification of UPRA. We observed that (i) the 17 feature variables extracted in this study yielded a high area under the receiver operating characteristic curve of 0.75 using the ANN model and that (ii) the ANN exhibited better AUC (0.73) than the CNN (0.50), and (iii) a ready and available app for predicting UHA was developed. The app could help clinicians predict UPRA of patients with pneumonia at an early stage and enable them to formulate preparedness plans near or after patient discharge from hospitalization.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2762
Author(s):  
Samantha Di Donato ◽  
Alessia Vignoli ◽  
Chiara Biagioni ◽  
Luca Malorni ◽  
Elena Mori ◽  
...  

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.


Author(s):  
Jianhua Xu ◽  
Guyu Sun ◽  
Wei Cao ◽  
Wenyuan Fan ◽  
Zhihao Pan ◽  
...  

AbstractThe Covid-19 pandemic has given rise to stigma, discrimination, and even hate crimes against various populations in the Chinese language–speaking world. Using interview data with victims, online observation, and the data mining of media reports, this paper investigated the changing targets of stigma from the outbreak of Covid-19 to early April 2020 when China had largely contained the first wave of Covid-19 within its border. We found that at the early stage of the pandemic, stigma was inflicted by some non-Hubei Chinese population onto Wuhan and Hubei residents, by some Hong Kong and Taiwan residents onto mainland Chinese, and by some Westerners towards overseas Chinese. With the number of cases outside China surpassing that in China, stigmatization was imposed by some Chinese onto Africans in China. We further explore how various factors, such as the fear of infection, food and mask culture, political ideology, and racism, affected the stigmatization of different victim groups. This study not only improved our understanding of how stigmatization happened in the Chinese-speaking world amid Covid-19 but also contributes to the literature of how sociopolitical factors may affect the production of hate crimes.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Janhavi R. Raut ◽  
Ben Schöttker ◽  
Bernd Holleczek ◽  
Feng Guo ◽  
Megha Bhardwaj ◽  
...  

AbstractCirculating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50–75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498–0.616) for the ERS and 0.622 (0.564–0.681) for the PRS.


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