A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of Chemotherapy

In order to accurately predict oncological outcomes of colorectal cancer (CRC), we established a risk signature with tumor infiltrating neutrophils and T immune cells for prognosis. A total of 276 CRC patients from FUSCC, and 434 patients from TCGA cohort were enrolled in the study. A risk signature...

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Main Authors: Xiang Hu, Ya-Qi Li, Xiao-ji Ma, Long Zhang, San-Jun Cai, Jun-Jie Peng
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2019.00704/full
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author Xiang Hu
Xiang Hu
Ya-Qi Li
Ya-Qi Li
Xiao-ji Ma
Xiao-ji Ma
Long Zhang
Long Zhang
San-Jun Cai
San-Jun Cai
Jun-Jie Peng
Jun-Jie Peng
author_facet Xiang Hu
Xiang Hu
Ya-Qi Li
Ya-Qi Li
Xiao-ji Ma
Xiao-ji Ma
Long Zhang
Long Zhang
San-Jun Cai
San-Jun Cai
Jun-Jie Peng
Jun-Jie Peng
author_sort Xiang Hu
collection DOAJ
description In order to accurately predict oncological outcomes of colorectal cancer (CRC), we established a risk signature with tumor infiltrating neutrophils and T immune cells for prognosis. A total of 276 CRC patients from FUSCC, and 434 patients from TCGA cohort were enrolled in the study. A risk signature model in combination with CEACAM8+ neutrophils, CD3+, CD8+ T lymphocytes, and FOXP3+ regulatory T cells was established, and the relationships with patient clinicopathological characteristics and prognosis were evaluated. In TCGA cohort, high CEACAM8 expression was observed as an independent factor of poor disease-free survival (DFS), as well as inversely correlated with CD8 (P = 0.0035) and FOXP3 expression (P = 0.05). In the FUSCC cohort for validation, the association between CEACAM8+ neutrophils and DFS had been confirmed in CRC tissue (P = 0.026). Furthermore, a risk stratification was derived from integration of CEACAM8+ neutrophils and T immune cells. In both OS and DFS, the high-risk group all demonstrated worse prognosis than low-risk group, with statistical significance (all P < 0.001). In addition, the high-risk group was correlated with post-operative relapses with accurate prediction. Furthermore, the high-risk group identified a subgroup of CRC patients who appeared not to benefit from adjuvant chemotherapy. At last, predictive nomograms were constructed with recognized independent prognosticators, showing this risk signature increasing the predictive accuracy and efficiency for OS and DFS. In conclusion, incorporation of neutrophil into T lymphocytes could provide more accurate prognostic information in CRC, and this risk stratification predicted for survival benefit from post-operative chemotherapy.
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spelling doaj.art-5df71d24e69b40eba6e7e54ab5a4fe842022-12-22T02:09:29ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-08-01910.3389/fonc.2019.00704420646A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of ChemotherapyXiang Hu0Xiang Hu1Ya-Qi Li2Ya-Qi Li3Xiao-ji Ma4Xiao-ji Ma5Long Zhang6Long Zhang7San-Jun Cai8San-Jun Cai9Jun-Jie Peng10Jun-Jie Peng11Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaIn order to accurately predict oncological outcomes of colorectal cancer (CRC), we established a risk signature with tumor infiltrating neutrophils and T immune cells for prognosis. A total of 276 CRC patients from FUSCC, and 434 patients from TCGA cohort were enrolled in the study. A risk signature model in combination with CEACAM8+ neutrophils, CD3+, CD8+ T lymphocytes, and FOXP3+ regulatory T cells was established, and the relationships with patient clinicopathological characteristics and prognosis were evaluated. In TCGA cohort, high CEACAM8 expression was observed as an independent factor of poor disease-free survival (DFS), as well as inversely correlated with CD8 (P = 0.0035) and FOXP3 expression (P = 0.05). In the FUSCC cohort for validation, the association between CEACAM8+ neutrophils and DFS had been confirmed in CRC tissue (P = 0.026). Furthermore, a risk stratification was derived from integration of CEACAM8+ neutrophils and T immune cells. In both OS and DFS, the high-risk group all demonstrated worse prognosis than low-risk group, with statistical significance (all P < 0.001). In addition, the high-risk group was correlated with post-operative relapses with accurate prediction. Furthermore, the high-risk group identified a subgroup of CRC patients who appeared not to benefit from adjuvant chemotherapy. At last, predictive nomograms were constructed with recognized independent prognosticators, showing this risk signature increasing the predictive accuracy and efficiency for OS and DFS. In conclusion, incorporation of neutrophil into T lymphocytes could provide more accurate prognostic information in CRC, and this risk stratification predicted for survival benefit from post-operative chemotherapy.https://www.frontiersin.org/article/10.3389/fonc.2019.00704/fulltumor CEACAM8+ neutrophiltumor-infiltrating lymphocytescolorectal cancerrisk signaturesurvival analysis
spellingShingle Xiang Hu
Xiang Hu
Ya-Qi Li
Ya-Qi Li
Xiao-ji Ma
Xiao-ji Ma
Long Zhang
Long Zhang
San-Jun Cai
San-Jun Cai
Jun-Jie Peng
Jun-Jie Peng
A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of Chemotherapy
Frontiers in Oncology
tumor CEACAM8+ neutrophil
tumor-infiltrating lymphocytes
colorectal cancer
risk signature
survival analysis
title A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of Chemotherapy
title_full A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of Chemotherapy
title_fullStr A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of Chemotherapy
title_full_unstemmed A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of Chemotherapy
title_short A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of Chemotherapy
title_sort risk signature with inflammatory and t immune cells infiltration in colorectal cancer predicting distant metastases and efficiency of chemotherapy
topic tumor CEACAM8+ neutrophil
tumor-infiltrating lymphocytes
colorectal cancer
risk signature
survival analysis
url https://www.frontiersin.org/article/10.3389/fonc.2019.00704/full
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