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      Evaluating the predictive performance of gut microbiota for the early-stage colorectal cancer

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          Abstract

          Background

          Colorectal cancer (CRC) has been regarded as one of the most frequently diagnosed malignancies among the leading causes of cancer-related morbidity and mortality globally. Diagnosis of CRC at the early-stages of tumour might improve the survival rate of patients. The current study sought to determine the performance of fecal Fusobacterium nucleatum ( F. nucleatum) and Streptococcus bovis ( S. bovis) for timely predicting CRC.

          Methods

          Through a case–control study, the fecal sample information of 83 individuals (38 females, 45 males) referring to a hospital in Tehran, Iran was used. All patients underwent a complete colonoscopy, regarded as a gold standard test. Bacterial species including S. bovis and F. nucleatum were measured by absolute quantitative real-time PCR. The Bayesian univariate and bivariate latent class models (LCMs) were applied to estimate the ability of the candidate bacterial markers in order to early detection of patients with CRC.

          Results

          Bayesian univariate LCMs demonstrated that the sensitivities of S. bovis and F. nucleatum were estimated to be 86% [95% credible interval (CrI) 0.82–0.91] and 82% (95% CrI 0.75–0.88); while specificities were 84% (95% CrI 0.78–0.89) and 80% (95% CrI 0.73–0.87), respectively. Moreover, the area under the receiver operating characteristic curves (AUCs) were 0.88 (95% CrI 0.83–0.94) and 0.80 (95% CrI 0.73–0.85) respectively for S. bovis and F. nucleatum. Based on the Bayesian bivariate LCMs, the sensitivities of S. bovis and F. nucleatum were calculated as 93% (95% CrI 0.84–0.98) and 90% (95% CrI 0.85–0.97), the specificities were 88% (95% CrI 0.78–0.93) and 87% (95% CrI 0.79–0.94); and the AUCs were 0.91 (95% CrI 0.83–0.99) and 0.88(95% CrI 0.81–0.96), respectively.

          Conclusions

          Our data has identified that according to the Bayesian bivariate LCM, S. bovis and F. nucleatum had a more significant predictive accuracy compared with the univariate model. In summary, these intestinal bacteria have been highlighted as novel tools for early-stage CRC diagnosis.

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          Most cited references46

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          Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors

          According to GLOBOCAN 2018 data, colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. Nearly 2 million new cases and about 1 million deaths are expected in 2018. CRC incidence has been steadily rising worldwide, especially in developing countries that are adopting the “western” way of life. Obesity, sedentary lifestyle, red meat consumption, alcohol, and tobacco are considered the driving factors behind the growth of CRC. However, recent advances in early detection screenings and treatment options have reduced CRC mortality in developed nations, even in the face of growing incidence. Genetic testing and better family history documentation can enable those with a hereditary predisposition for the neoplasm to take preventive measures. Meanwhile, the general population can reduce their risk by lowering their red meat, alcohol, and tobacco consumption and raising their consumption of fibre, wholesome foods, and certain vitamins and minerals.
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            Global colorectal cancer burden in 2020 and projections to 2040

            • There are estimated 1.93 million new CRC cases diagnosed, and 0.94 million CRC caused deaths in 2020 worldwide. • The global new CRC cases is predicted to reach 3.2 million in 2040. • China and the United States have the highest estimated number of new CRC cases in the next 20 years. • The number of new CRC cases is increased from 0.56 million (2020) to 0.91 million (2040) in China. • The number of new CRC cases is increased from 0.16 million (2020) to 0.21 million (2040) in the United States. As the third most common malignancy and the second most deadly cancer, colorectal cancer (CRC) induces estimated 1.9 million incidence cases and 0.9 million deaths worldwide in 2020. The incidence of CRC is higher in highly developed countries, and it is increasing in middle- and low-income countries due to westernization. Moreover, a rising incidence of early-onset CRC is also emerging. The large number of CRC cases poses a growing global public health challenge. Raising awareness of CRC is important to promote healthy lifestyle choices, novel strategies for CRC management, and implementation of global screening programs, which are critical to reducing CRC morbidity and mortality in the future. CRC is a heterogeneous disease, and its subtype affiliation influences prognosis and therapeutic response. An accurate CRC subtype classification system is of great significance for basic research and clinical outcome. Here, we present the global epidemiology of CRC in 2020 and projections for 2040, review the major CRC subtypes to better understand CRC molecular basis, and summarize current risk factors, prevention, and screening strategies for CRC.
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              Gut microbiota in colorectal cancer: mechanisms of action and clinical applications

              Colorectal cancer (CRC) accounts for about 10% of all new cancer cases globally. Located at close proximity to the colorectal epithelium, the gut microbiota comprises a large population of microorganisms that interact with host cells to regulate many physiological processes, such as energy harvest, metabolism and immune response. Sequencing studies have revealed microbial compositional and ecological changes in patients with CRC, whereas functional studies in animal models have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis. These findings give new opportunities to take advantage of our knowledge on the gut microbiota for clinical applications, such as gut microbiota analysis as screening, prognostic or predictive biomarkers, or modulating microorganisms to prevent cancer, augment therapies and reduce adverse effects of treatment. This Review aims to provide an overview and discussion of the gut microbiota in colorectal neoplasia, including relevant mechanisms in microbiota-related carcinogenesis, the potential of utilizing the microbiota as CRC biomarkers, and the prospect for modulating the microbiota for CRC prevention or treatment. These scientific findings will pave the way to clinically translate the use of gut microbiota for CRC in the near future.
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                Author and article information

                Contributors
                maedeh.amini92@yahoo.com
                amin_phg@yahoo.com
                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central (London )
                1471-230X
                12 December 2022
                12 December 2022
                2022
                : 22
                : 514
                Affiliations
                [1 ]GRID grid.411600.2, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran
                [2 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Section Mass Spectrometry and Proteomics, Institute of Clinical Chemistry and Laboratory Medicine, , University Medical Center Hamburg-Eppendorf (UKE), ; Hamburg, Germany
                [3 ]GRID grid.411600.2, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran
                Article
                2599
                10.1186/s12876-022-02599-x
                9743636
                36510191
                13d1e4b8-3fc8-42c4-bed8-0496b8284412
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 24 August 2022
                : 30 November 2022
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Gastroenterology & Hepatology
                colorectal cancer,intestinal microbiota,f. nucleatum,s. bovis,bayesian approach,receiver operator characteristic curve,latent class analysis

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