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  • br Findings We established a prognostic panel designated as

    2019-11-12


    Findings: We established a prognostic panel, designated as tumour microenvironment risk score (TMRS), consisting of 100 genes. With specific risk score formulae, the TMRS panel possesses a strong ability to predict relapse-free survival and overall survival through both univariate and multivariate analyses. Compared with the TNM stage, the TMRS panel showed much higher predictive accuracy. Further analysis revealed that patients with higher TMRS scores exhibited no therapeutic benefits from adjuvant chemotherapy, probably due to the ac-tivation of stromal relevant pathways and infiltration of stromal cells. Besides colon cancer, the TMRS panel was also revealed to be a reliable tool for prognostic prediction and chemotherapeutic decision-making in gastric can-cer. Its value in predicting immunotherapy outcomes was also confirmed in two other cohorts consisting of met-astatic urothelial carcinoma patients and melanoma patients.
    Interpretation: Our TMRS panel may be an effective tool for survival prediction and treatment guidance in patients with stage I–III colon cancer. Fund: This work was supported by the National Natural Science Foundation of China (No. 81772580) and Guang-zhou Planed Project of Science and Technology (No. 201803010070).
    © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
    1. Introduction
    Colon cancer is a major source of morbidity and mortality worldwide CORM-3 [1]. Currently, the AJCC staging system and histologic classification re-main the most important guidelines for stratifying patients and making clinical decisions [2]. However, due to the high levels of heterogeneity found in colon cancer, prognoses may vary widely between patients with similar clinical features. Therefore, in order to stratify patients
    Corresponding authors at: Department of Oncology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, PR China.
    more precisely, it CORM-3 becomes necessary to consider other prognostic fac-tors in addition to clinical factors.
    The tumour microenvironment (TME), consisting of multiple im-mune cells and stromal cells, is critical for the regulation of cancer initi-ation and development as well as cellular response to chemotherapy [3,4]. In recent years, the rise of immunotherapy, including immune checkpoint inhibitors, has shown assessment of TME landscape hetero-geneity and reshaping of immune microenvironment to be promising avenues for future cancer management [5]. In colon cancer, assessing amounts of tumour-infiltrating lymphocytes based on IHC staining of CD3 and CD8, via an “immunoscore”, is considered an important supple-mental marker in the TNM staging system for relapse and mortality pre-diction [6,7]. Unfortunately, the accuracy of prognosis prediction using
    Research in context
    Evidence before this study
    The heterogeneity of tumour microenvironment (TME) contains multiple dimensions of information on patient prognosis and treat-ment response. Currently, several signatures based on TME genes have been reported. However, as the genes included in these sig-natures were not all correlated with prognosis, the clinical practi-cality of these signatures was not satisfactory. In colon cancer, recent advances in high-throughput gene testing technology have led to the development of some molecular signatures for prognosis prediction and personalisation of treatment paradigms. However, to the best of our knowledge, none of these signatures were established based on TME-relevant genes. In addition, an immunoscore system has been developed based on IHC staining of CD3 and CD8. Unfortunately, the accuracy of prognosis predic-tion using the immunoscore system was found to be limited, as re-ported by the latest multi-central clinical research. Therefore, it is necessary to.