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      A nomogram based on pretreatment levels of serum bilirubin and total bile acid levels predicts survival in colorectal cancer patients

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          Abstract

          Background

          Serum bilirubin and total bile acid (TBA) levels have been reported to be strongly associated with the risk and prognosis of certain cancers. Here, we aimed to investigate the effects of pretreatment levels of serum bilirubin and bile acids on the prognosis of patients with colorectal cancer (CRC).

          Methods

          A retrospective cohort of 1474 patients with CRC who underwent surgical resection between January 2015 and December 2017 was included in the study. Survival analysis was used to evaluate the predictive value of pretreatment levels of bilirubin and bile acids. X-Tile software was used to identify optimal cut-off values for total bilirubin (TBIL), direct bilirubin (DBIL) and TBA in terms of overall survival (OS) and disease-free survival (DFS).

          Results

          DBIL, TBIL, and TBA were validated as significant prognostic factors by univariate Cox regression analysis for both 3-year OS and DFS. Multivariate Cox regression analyses confirmed that high DBIL, TBIL and TBA levels were independent prognostic factors for both OS (HR: 0.435, 95% CI: 0.299–0.637, P < 0.001; HR: 0.436, 95% CI: 0.329–0.578, P < 0.001; HR: 0.206, 95% CI: 0.124–0.341, P < 0.001, respectively) and DFS (HR: 0.583, 95% CI: 0.391–0.871, P = 0.008; HR:0.437,95% CI: 0.292–0.655, P <0.001; HR: 0.634, 95% CI: 0.465–0.865, P = 0.004, respectively). In addition, nomograms for OS and DFS were established according to all significant factors, and the c-indexes were 0.819 (95% CI: 0.806–0.832) and 0.835 (95% CI: 0.822–0.849), respectively.

          Conclusions

          TBIL, DBIL and TBA levels are independent prognostic factors in colorectal cancer patients. The nomograms based on OS and DFS can be used as a practical model for evaluating the prognosis of CRC patients.

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          Most cited references26

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          Cancer treatment and survivorship statistics, 2019

          The number of cancer survivors continues to increase in the United States because of the growth and aging of the population as well as advances in early detection and treatment. To assist the public health community in better serving these individuals, the American Cancer Society and the National Cancer Institute collaborate every 3 years to estimate cancer prevalence in the United States using incidence and survival data from the Surveillance, Epidemiology, and End Results cancer registries; vital statistics from the Centers for Disease Control and Prevention's National Center for Health Statistics; and population projections from the US Census Bureau. Current treatment patterns based on information in the National Cancer Data Base are presented for the most prevalent cancer types. Cancer-related and treatment-related short-term, long-term, and late health effects are also briefly described. More than 16.9 million Americans (8.1 million males and 8.8 million females) with a history of cancer were alive on January 1, 2019; this number is projected to reach more than 22.1 million by January 1, 2030 based on the growth and aging of the population alone. The 3 most prevalent cancers in 2019 are prostate (3,650,030), colon and rectum (776,120), and melanoma of the skin (684,470) among males, and breast (3,861,520), uterine corpus (807,860), and colon and rectum (768,650) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost two-thirds (64%) are aged 65 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by follow-up care providers. Although there are growing numbers of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care.
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            X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization.

            The ability to parse tumors into subsets based on biomarker expression has many clinical applications; however, there is no global way to visualize the best cut-points for creating such divisions. We have developed a graphical method, the X-tile plot that illustrates the presence of substantial tumor subpopulations and shows the robustness of the relationship between a biomarker and outcome by construction of a two dimensional projection of every possible subpopulation. We validate X-tile plots by examining the expression of several established prognostic markers (human epidermal growth factor receptor-2, estrogen receptor, p53 expression, patient age, tumor size, and node number) in cohorts of breast cancer patients and show how X-tile plots of each marker predict population subsets rooted in the known biology of their expression.
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              Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis

              Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of recent research progress in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also highlight the strategies and cutting-edge technologies to target gut-microbiota-dependent alterations in bile acid metabolism in the context of cancer therapy.
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                Author and article information

                Contributors
                gracefulliuly@163.com
                caikailin@hust.edu.cn
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                21 January 2021
                21 January 2021
                2021
                : 21
                : 85
                Affiliations
                [1 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Gastrointestinal Surgery, , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, ; 1277 JieFang Avenue, Wuhan, 430022 Hubei China
                [2 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Gastrointestinal Surgery, , The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, ; Wuhan, China
                [3 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Pathology, , Union Hospital, Tongji Medical, Huazhong University of Science and Technology, ; Wuhan, 430022 Hubei China
                [4 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Epidemiology and Biostatistics, the Ministry of Education Key Lab of Environment and Health, , School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, ; Wuhan, Hubei 430022 China
                Author information
                http://orcid.org/0000-0002-2572-0907
                Article
                7805
                10.1186/s12885-021-07805-9
                7818769
                33478423
                ef9b72fd-c070-49a4-91b0-ec8af9be4662
                © The Author(s) 2021

                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
                : 21 July 2020
                : 11 January 2021
                Funding
                Funded by: the Graduates’ Innovation Fund, Huazhong University of Science and Technology
                Award ID: No. 2020yjsCXCY055
                Award Recipient :
                Funded by: Free innovation pre-research fund and platform scientific research fund in 2019
                Award ID: 02.03.2019-111
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                colorectal cancer,total bilirubin,direct bilirubin,total bile acid,survival analysis

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