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      Comprehensive comparative analysis of prognostic value of serum systemic inflammation biomarkers for colorectal cancer: Results from a large multicenter collaboration

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          Abstract

          Background

          The incidence of colorectal cancer (CRC) is common and reliable biomarkers are lacking. We aimed to systematically and comprehensively compare the ability of various combinations of serum inflammatory signatures to predict the prognosis of CRC. Moreover, particular attention has been paid to the clinical feasibility of the newly developed inflammatory burden index (IBI) as a prognostic biomarker for CRC.

          Methods

          The discrimination capacity of the biomarkers was compared using receiver operating characteristic curves and Harrell’s C-index. Kaplan-Meier curves and log-rank tests were used to compare survival differences between the groups. Cox proportional hazard regression analysis was used to determine the independent prognostic factors. Logistic regression analysis was used to assess the relationship between IBI, short-term outcomes, and malnutrition.

          Results

          IBI had the optimal prediction accuracy among the systemic inflammation biomarkers for predicting the prognosis of CRC. Taking IBI as a reference, none of the remaining systemic inflammation biomarkers showed a gain. Patients with high IBI had significantly worse overall survival than those with low IBI (56.7% vs. 80.2%; log-rank P<0.001). Multivariate Cox regression analysis showed that continuous IBI was an independent risk factor for the prognosis of CRC patients (hazard ratio = 1.165, 95% confidence interval [CI] = 1.043–1.302, P<0.001). High IBI was an independent risk factor for short-term outcomes (odds ratio [OR] = 1.537, 95% CI = 1.258–1.878, P<0.001), malnutrition (OR = 2.996, 95% CI = 1.471–6.103, P=0.003), and recurrence (OR = 1.744, 95% CI = 1.176–2.587, p = 0.006) in CRC patients.

          Conclusions

          IBI, as a reflection of systemic inflammation, is a feasible and promising biomarker for assessing the prognosis of CRC patients.

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          Most cited references26

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          Cancer statistics, 2022

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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            Cancer-related inflammation.

            The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
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              The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

              The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                05 January 2023
                2022
                : 13
                : 1092498
                Affiliations
                [1] 1 Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University , Beijing, China
                [2] 2 Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition , Beijing, China
                [3] 3 Key Laboratory of Cancer FSMP for State Market Regulation , Beijing, China
                [4] 4 Department of Geriatric Respiratory Medicine, The First Affiliated Hospital, Guangxi Medical University, Nanning , Guangxi, China
                [5] 5 Clinical Nutrition Department, Sichuan University West China Hospital, Chengdu , Sichuan, China
                Author notes

                Edited by: Carlos Pérez-Plasencia, National Autonomous University of Mexico, Mexico

                Reviewed by: Dipendra Khadka, Wonkwang University School of Medicine, South Korea; Tai Hato, Saitama Medical University, Japan

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.1092498
                9849562
                36685502
                ca62ae4e-0549-4036-b8ac-414f1f7e6b73
                Copyright © 2023 Xie, Ruan, Wei, Zhang, Ge, Zhang, Song, Zhang, Liu, Lin, Yang, Hu, Tang, Deng, Hu and Shi

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 November 2022
                : 06 December 2022
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 26, Pages: 10, Words: 4110
                Funding
                Funded by: National Key Research and Development Program of China , doi 10.13039/501100012166;
                Award ID: No. 2022YFC2009600, No. 2017YFC1309200
                Funded by: Beijing Municipal Science and Technology Commission , doi 10.13039/501100009592;
                Categories
                Immunology
                Original Research

                Immunology
                systemic inflammation,inflammatic burden index,colorectal cancer,prognosis,biomarker,malnutrition

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