A nomogram‑based immunoprofile predicts clinical outcomes for stage II and III human colorectal cancer

Wang,Lingxiong; Chang,Nijia; Wu,Liangliang; Li,Jinfeng; Zhang,Lijun; Chen,Yin; Zhou,Zhou; Hao,Jianqing; Wang,Qiong; Jiao,Shunchang

doi:10.3892/mco.2021.2419

A nomogram‑based immunoprofile predicts clinical outcomes for stage II and III human colorectal cancer

Authors:
- Lingxiong Wang
- Nijia Chang
- Liangliang Wu
- Jinfeng Li
- Lijun Zhang
- Yin Chen
- Zhou Zhou
- Jianqing Hao
- Qiong Wang
- Shunchang Jiao
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Affiliations: Institute of Oncology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Oncology, The Second Medical Centre, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Pneumology, Qingyang People's Hospital, Qingyang, Gansu 745000, P.R. China, Department of Pathology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Oncology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100853, P.R. China
Published online on: October 14, 2021 https://doi.org/10.3892/mco.2021.2419
Article Number: 257
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

An immunoscore for colorectal cancer (CRC) has higher prognostic significance than the TNM staging system. However, the tumor immune microenvironment contains various components that affect clinical prognosis. Therefore, a broader range of immune markers is required to establish an accurate immunoprofile to assess the prognosis of patients with CRC. Using immunohistochemistry combined with multispectral immunohistochemistry and objective assessments, the infiltration of four immune cell types (CD4⁺/CD8⁺/forkhead box p3⁺/CD33⁺ cells), as well as the expression of six co‑signaling molecules [programmed cell death 1 (PD1) ligand 1/PD1/T‑cell immunoglobulin mucin family member 3/lymphocyte‑activating 3/tumor necrosis factor receptor superfamily, member 4/inducible T‑cell costimulator] and indoleamine 2,3‑dioxygenase 1 were investigated in two independent cohorts of CRC. The patients' overall survival (OS) was evaluated using the Kaplan‑Meier method. Using the Cox proportional hazards model, independent prognostic factors of patients were assessed and a nomogram‑based immunoprofile system was developed. The predictive ability of the nomogram was determined using a concordance index (C‑index) and calibration curve. To facilitate clinical application, a simplified nomogram‑based immunoprofile was constructed. Using receiver operating characteristic (ROC) analysis, the predictive accuracy for OS was compared between the immunoprofile and the TNM staging system for patients with stage II/III CRC. According to multivariate analysis for the primary cohort, independent prognostic factors for OS were CD8⁺ tumor‑infiltrating lymphocytes, CD33⁺ myeloid‑derived suppressor cells and TNM stage, which were included in the nomogram. The C‑index of the nomogram for predicting OS was 0.861 (95% CI: 0.796‑0.925) for the internal validation and 0.759 (95% CI: 0.714‑0.804) for the external validation cohort. The simplified nomogram‑based immunoprofile system was able to separate same‑stage patients into different risk subgroups, particularly for TNM stage II (P<0.0001) and III (P=0.0002) patients. Pairwise comparison of ROC curves for the immunoprofile and TNM stage systems for patients with stage II/III CRC revealed statistically significant differences (P=0.046) and the Z‑statistic value was 1.995. In conclusion, the nomogram‑based immunoprofile system provides prognostic accuracy regarding clinical outcomes and is a useful supplement to the TNM staging system for patients with stage II/III CRC.

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