Identification of microbial markers across populations in early detection of colorectal cancer

AbstractAssociations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-l-glycero-beta-d-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.

Download Full-text

Integrated analysis reveals five potential ceRNA biomarkers in human lung adenocarcinoma

PeerJ ◽

10.7717/peerj.6694 ◽

2019 ◽

Vol 7 ◽

pp. e6694 ◽

Cited By ~ 7

Author(s):

Yu Liu ◽

Deyao Xie ◽

Zhifeng He ◽

Liangcheng Zheng

Keyword(s):

Gene Expression ◽

Functional Analysis ◽

Transcription Factor ◽

Early Diagnosis ◽

Lung Adenocarcinoma ◽

Integrated Analysis ◽

Aberrant Expression ◽

Ontology Term ◽

Tumor Stages ◽

Potential Biomarkers

Background Competing endogenous RNAs (ceRNAs) are a newly identified type of regulatory RNA. Accumulating evidence suggests that ceRNAs play an important role in the pathogenesis of diseases such as cancer. Thus, ceRNA dysregulation may represent an important molecular mechanism underlying cancer progression and poor prognosis. In this study, we aimed to identify ceRNAs that may serve as potential biomarkers for early diagnosis of lung adenocarcinoma (LUAD). Methods We performed differential gene expression analysis on TCGA-LUAD datasets to identify differentially expressed (DE) mRNAs, lncRNAs, and miRNAs at different tumor stages. Based on the ceRNA hypothesis and considering the synergistic or feedback regulation of ceRNAs, a lncRNA–miRNA–mRNA network was constructed. Functional analysis was performed using gene ontology term and KEGG pathway enrichment analysis and KOBAS 2.0 software. Transcription factor (TF) analysis was carried out to identify direct targets of the TFs associated with LUAD prognosis. Identified DE genes were validated using gene expression omnibus (GEO) datasets. Results Based on analysis of TCGA-LUAD datasets, we obtained 2,610 DE mRNAs, 915 lncRNAs, and 125 miRNAs that were common to different tumor stages (|log2(Fold change)| ≥ 1, false discovery rate < 0.01), respectively. Functional analysis showed that the aberrantly expressed mRNAs were closely related to tumor development. Survival analyses of the constructed ceRNA network modules demonstrated that five of them exhibit prognostic significance. The five ceRNA interaction modules contained one lncRNA (FENDRR), three mRNAs (EPAS1, FOXF1, and EDNRB), and four miRNAs (hsa-miR-148a, hsa-miR-195, hsa-miR-196b, and hsa-miR-301b). The aberrant expression of one lncRNA and three mRNAs was verified in the LUAD GEO dataset. Transcription factor analysis demonstrated that EPAS1 directly targeted 13 DE mRNAs. Conclusion Our observations indicate that lncRNA-related ceRNAs and TFs play an important role in LUAD. The present study provides novel insights into the molecular mechanisms underlying LUAD pathogenesis. Furthermore, our study facilitates the identification of potential biomarkers for the early diagnosis and prognosis of LUAD and therapeutic targets for its treatment.

Download Full-text

A meta-analysis of proteomic blood markers of colorectal cancer

Current Medicinal Chemistry ◽

10.2174/0929867327666200427094054 ◽

2020 ◽

Vol 27 ◽

Author(s):

Xiang Chen ◽

Jiayu Sun ◽

Xue Wang ◽

Yumeng Yuan ◽

Leshan Cai ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Diagnosis ◽

Calcium Binding ◽

Early Stage ◽

Meta Analysis ◽

Bibliographic Databases ◽

Diagnostic Efficiency ◽

Case Control Studies ◽

Serum Proteomics ◽

Specificity And Sensitivity

Objective: Early diagnosis will significantly improve the survival rate of colorectal cancer (CRC); however, the existing methods for CRC screening were either invasive or inefficient. There is an emergency need for novel markers in CRC’s early diagnosis. Serum proteomics has gained great potential in discovering novel markers, providing markers that reflect the early stage of cancer and prognosis prediction of CRC. In this paper, the results of proteomics of CRC studies were summarized through a meta-analysis, to obtain the diagnostic efficiency of novel markers. Methods: A systematic search on bibliographic databases was performed to collect the studies that explore blood-based markers for CRC applying proteomics. The detection and validation methods, as well as the specificity and sensitivity of the biomarkers in these studies, were evaluated. Newcastle-Ottawa Scale (NOS) case-control studies version was used for quality assessment of included studies. Results: Thirty-four studies were selected from 751 studies, in which markers detected by proteomics were summarized. In total, fifty-nine proteins were classified according to their biological function. The sensitivity, specificity, or AUC varied among these markers. Among them, Mammalian STE20-like protein kinase 1/ Serine threonine kinase 4 (MST1/STK4), S100 calcium-binding protein A9 (S100A9), and Tissue inhibitor of metalloproteinases 1 (TIMP1) were suitable for effect sizes merging, and their diagnostic efficiencies were recalculated after merging. MST1/STK4 obtained a sensitivity of 68% and a specificity of 78%. S100A9 achieved a sensitivity of 72%, a specificity of 83%, and an AUC of 0.88. TIMP1 obtained a sensitivity of 42%, a specificity of 88%, and an AUC of 0.71. Conclusion: MST1/STK4, S100A9, and TIMP1 showed excellent performance for CRC detection. Several other markers also presented optimized diagnostic efficacy for CRC early detection, but further verification is still needed before they are suitable for clinical use. The discovering of more efficient markers will benefit CRC treatment.

Download Full-text

Front Cover: Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

PROTEOMICS ◽

10.1002/pmic.201970081 ◽

2019 ◽

Vol 19 (10) ◽

pp. 1970081

Author(s):

Putri‐Intan‐Hafizah Megat Mohd Azlan ◽

Siok‐Fong Chin ◽

Teck Yew Low ◽

Hui‐min Neoh ◽

Rahman Jamal

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Gut Microbiota ◽

Front Cover

Download Full-text

Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits

10.21203/rs.3.rs-400629/v1 ◽

2021 ◽

Author(s):

Hirotsugu Shiroma ◽

Satoshi Shiba ◽

Pande Putu Erawijantari ◽

Hiroyuki Takamaru ◽

Masayoshi Yamada ◽

...

Keyword(s):

Colorectal Cancer ◽

Random Forest ◽

Gut Microbiota ◽

Learning Algorithm ◽

Fusobacterium Nucleatum ◽

Shotgun Metagenomics ◽

Flight Mass Spectrometry ◽

Parvimonas Micra ◽

Increased Risk ◽

One Year

Abstract Background: Postoperative colorectal cancer (CRC) patients are at increased risk of developing metachronous CRC. Despite accumulating evidence indicating that the gut microbiota and metabolites can promote CRC carcinogenesis, the influence of surgery for CRC on the gut microbiota and metabolites remains partially understood. We hypothesized that if surgery does not eliminate the bacteria and metabolites promoting CRC carcinogenesis, these bacteria and metabolites might be associated with the development of metachronous CRC. To test this hypothesis, we collected 170 fecal samples from 85 CRC patients in pre- and approximately one year postsurgery status, and performed shotgun metagenomics sequencing and capillary electrophoresis time-of-flight mass spectrometry-based metabolomics analyses and compared pre- and postsurgery status.Results: CRC-associated bacteria such as Parvimonas micra and Fusobacterium nucleatum were significantly (P < 0.005) decreased after surgery. On the other hand, cholate, carcinogenesis-associated deoxycholate, its biotransformed genes (bai operon) from cholate to deoxycholate, and the contributing bacterium (Clostridium scindens) were significantly (P < 0.005) increased. Additionally, these alterations were only observed in postleft surgery. Cholate and glycocholate were significantly (P < 0.005) increased in postright surgery. We also developed a method for potential CRC risk assessment based on the gut microbiota and metabolomic compositions using a random forest machine learning algorithm and then applied it to postoperative patients. The estimated CRC risk based on the random forest algorithm was partially restored postsurgery. Conclusions: Our results indicate that the high potential CRC risk in CRC postoperative patients is associated with metabolites derived from the gut microbiota, which targets interventions to reduce the CRC risk.

Download Full-text

The Experiences of Early Detection, Early Diagnosis and Early Treatment of Cancer in Rural Areas of China

Journal of Global Oncology ◽

10.1200/jgo.18.60300 ◽

2018 ◽

Vol 4 (Supplement 2) ◽

pp. 49s-49s

Author(s):

J. Li ◽

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Early Diagnosis ◽

Early Treatment ◽

Rural Areas ◽

Antibody Detection ◽

Transfer Payment ◽

High Risk Population ◽

Screening Methods ◽

Expert Committee

Background: The cancers of the lung, liver, stomach, esophagus, colorectum and nasopharynx account for more than 70% of the causes of cancer death, making them the major cancer burdens in China. The early detection and treatment of cancers including lung, liver, stomach, esophagus, colorectum and nasopharynx was supported by the central government special financial transfer payment in the rural areas in 2006-2017. Aim: To improve the efficiency of early diagnosis and early treatment to reduce cancer mortality and incidence in the population in China. Methods: Cancer screening methods developed by Group of Expert Committee of Cancer Foundation of China were used, including digestive tract endoscopy for stomach and esophageal and colorectal cancer, LDCT for lung cancer, AFP and abdominal ultrasound for liver cancer, EB virus antibody detection and nasal endoscopy for nasopharyngeal carcinoma. Results: Among the cancers of lung, liver, stomach, esophagus, colorectum and nasopharynx, the screening high risk population were 55,363; 126,443; 103,3036; 1,425,642; 252,911; and 79,726 respectively; and the screening detection rates of precancerous lesions and cancer were 0.62%, 0.66%, 0.87%, 1.62%, 5.29% and 0.49% respectively; and the early diagnosis rates were 47.80%, 60.86%, 71.24%, 73.38%, 91.85% and 64.43% respectively; and the treatment rates were 83.28%, 90.33%, 87.94%, 82.91%, 94.04% and 95.88% respectively. Conclusion: The programs for early detection and early treatment of colorectal cancer and esophageal cancer demonstrated a promising benefit, which should be generalized to broad population implementation.

Download Full-text

Management of patients with early-stage colon cancer: guidelines of the Italian Medical Oncology Association

ESMO Open ◽

10.1136/esmoopen-2020-001001 ◽

2020 ◽

Vol 5 (6) ◽

pp. e001001

Author(s):

Lisa Salvatore ◽

Marco Imperatori ◽

Ermenegildo Arnoldi ◽

Carlo Carnaghi ◽

Stefano Cordio ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Early Diagnosis ◽

Medical Oncology ◽

Radical Surgery ◽

Early Stage ◽

Colorectal Cancers ◽

Early Stage Colon Cancer ◽

Cancer Guidelines

About 75% of colorectal cancers are diagnosed as early stage, in which radical surgery is achievable. In the last decade, in Italy, the overall incidence of colorectal cancer has remained stable, while mortality gradually decreased, which is attributable to early diagnosis and improved medical, surgical and locoregional treatments. The Italian Medical Oncology Association formulated guidelines to manage early-stage colon cancer, including screening, diagnosis, treatment and follow-up, which we herein present.

Download Full-text

Gut microbiota and colorectal cancer: insights into pathogenesis for novel therapeutic strategies

Zeitschrift für Gastroenterologie ◽

10.1055/s-0043-116387 ◽

2017 ◽

Vol 55 (09) ◽

pp. 872-880 ◽

Cited By ~ 2

Author(s):

Yongbo Kang ◽

Wei Pan ◽

Yue Cai

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Early Stage ◽

Bacterial Flora ◽

Oral Intake ◽

Protective Role ◽

Experimental Models ◽

Microbial Strains ◽

Novel Therapeutic Strategies ◽

Specific Species

AbstractColorectal cancer (CRC), as a leading cause of cancer-related death, is triggered by the complex interplay of host genetics and environmental factors. Mounting evidence has shed light on the association of the gut microbiota dysbiosis with CRC. In CRC experimental models, certain gut microbial strains have been shown to inhibit or attenuate immune responses, indicating that specific species among intestinal commensal bacteria may play either a pathogenic or a protective role in the development of CRC. Oral intake of probiotics/prebiotics can therefore serve as a therapeutic approach for CRC treatment. Microbiota studies in cancer, however, are still at the early stage, lack of quantitative data for clinic application. Fortunately, sequencing-based technologies are a boon to further investigation on the association of the intestinal bacterial flora and human diseases. This review considers the evidence for the role of the gut microbiota in CRC development and progression, responsiveness to immune system, and the related therapeutic applications of probiotics/prebiotics.

Download Full-text

Integrated analysis of the faecal metagenome and serum metabolome reveals the role of gut microbiome-associated metabolites in the detection of colorectal cancer and adenoma

Gut ◽

10.1136/gutjnl-2020-323476 ◽

2021 ◽

pp. gutjnl-2020-323476

Author(s):

Feng Chen ◽

Xudong Dai ◽

Chang-Chun Zhou ◽

Ke-xin Li ◽

Yu-juan Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Adenoma ◽

Gut Microbiome ◽

Validation Cohort ◽

Early Stage ◽

Area Under The Curve ◽

Integrated Analysis ◽

Serum Metabolites ◽

Adenoma Detection ◽

Metagenome Sequencing

ObjectiveTo profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy individuals.DesignIntegrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort.ResultsIn total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93).ConclusionGut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection.

Download Full-text

The Importance of Molecular Diagnostics and Screening Programs in Monitoring and Evaluation of Colorectal Cancer in the Republic of North Macedonia

Sestrinski glasnik/Nursing Journal ◽

10.11608/sgnj.25.2.10 ◽

2020 ◽

Vol 25 (2) ◽

pp. 152-154

Author(s):

Jovanka Trpkovska ◽

Nevenka Velickova

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Early Stage ◽

Preventive Measure ◽

Morbidity And Mortality ◽

Care Staff ◽

Health Care Staff ◽

Surgical Removal ◽

Screening Programs ◽

The Republic

Colorectal cancer (CRC) is one of the most common malignant diseases (12 % of the total) that occurs with an incidence of 15 – 30 new cases per 100,000 population per year in European Union countries. The risk of this disease during life depends on many factors such as age, diet, physical activity, personal and family predisposition. Several preventive measures can reduce the number of colorectal cancer patients. First of all, the regular screening which allows the detection of precancerous polyps or cancer in the early stage and their successful surgical removal. The purpose of this paper is to highlight the importance of screening programs as a preventive measure for the early detection of colorectal cancer and to reduce the morbidity and mortality of this disease. The strategy for improving the early detection of colorectal cancer also implies availability of useful information about the importance of screening programs for everyone as well as educating health care staff about the program itself. Number of newly registered colorectal cancer cases in 2009 in the Republic North Macedonia stands at 547 with a rate of 26.7 compared to 2018 with 839 newly registered cases with a rate of 40.4 which clearly indicates an increasing trend of colorectal cancer. Multidisciplinary approach to early detection of colorectal cancer, continuity of Program funding and quality of services will lead to reduction of morbidity and mortality of this type of cancer.

Download Full-text

Chronic Kidney Disease Diagnosis using Decision Tree Algorithms

10.21203/rs.3.rs-34685/v1 ◽

2020 ◽

Author(s):

Hamida Ilyas ◽

Sajid Ali ◽

Mahvish Ponum ◽

Osman Hasan ◽

Muhammad Tahir Mahmood

Keyword(s):

Machine Learning ◽

Chronic Kidney Disease ◽

Random Forest ◽

Kidney Disease ◽

Early Detection ◽

Early Stage ◽

Disease Diagnosis ◽

Automated System ◽

Disease Epidemiology ◽

Machine Learning Classification

Abstract Chronic Kidney Disease (CKD), i.e., gradual decrease in the renal function spanning over a duration of several months to years without any major symptoms, is a life-threatening disease. It progresses in six stages according to the severity level. It is categorized into various stages based on the Glomerular Filtration Rate (GFR), which in turn utilizes several attributes, like age, sex, race and Serum Creatinine. Among multiple available models for estimating GFR value, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), which is a linear model, has been found to be quite efficient because it allows detecting all CKD stages i.e., early stage to the last stage of kidney failure. Early detection and cure of CKD is extremely desirable as it can lead to the prevention of unwanted consequences. Machine learning are being extensively advocated for early detection of symptoms and diagnosis of several diseases recently. With the same motivation, the aim of this study is to predict the various stages of CKD using machine learning classification algorithms on the dataset obtained from the medical records of affected people. In particular, we have used the Random Forest and J48 algorithms to obtain a sustainable and practicable model to detect various stages of CKD with comprehensive medical accuracy. Comparative analysis of the results revealed that J48 predicted CKD in all stages better than random forest with a 85.5% accuracy. The study also showed that J48 shows improved performance over Random Forest, so, it may be used to build an automated system for the detection of severity of CKD.

Download Full-text