Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer

Tumor-infiltrating immune cells (TIICs) play essential roles in cancer development and progression. However, the association of TIICs with prognosis in colorectal cancer (CRC) patients remains elusive. Infiltration of TIICs was assessed using ssGSEA and CIBERSORT tools. The association of TIICs with...

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Main Authors: Lele Ye, Teming Zhang, Zhengchun Kang, Gangqiang Guo, Yongji Sun, Kangming Lin, Qunjia Huang, Xinyu Shi, Zhonglin Ni, Ning Ding, Kong-Nan Zhao, Wenjun Chang, Junjie Wang, Feng Lin, Xiangyang Xue
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-10-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.02368/full
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author Lele Ye
Lele Ye
Teming Zhang
Zhengchun Kang
Gangqiang Guo
Yongji Sun
Kangming Lin
Qunjia Huang
Xinyu Shi
Zhonglin Ni
Ning Ding
Kong-Nan Zhao
Wenjun Chang
Junjie Wang
Feng Lin
Xiangyang Xue
author_facet Lele Ye
Lele Ye
Teming Zhang
Zhengchun Kang
Gangqiang Guo
Yongji Sun
Kangming Lin
Qunjia Huang
Xinyu Shi
Zhonglin Ni
Ning Ding
Kong-Nan Zhao
Wenjun Chang
Junjie Wang
Feng Lin
Xiangyang Xue
author_sort Lele Ye
collection DOAJ
description Tumor-infiltrating immune cells (TIICs) play essential roles in cancer development and progression. However, the association of TIICs with prognosis in colorectal cancer (CRC) patients remains elusive. Infiltration of TIICs was assessed using ssGSEA and CIBERSORT tools. The association of TIICs with prognosis was analyzed in 1,802 CRC data downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) and TCGA (https://portal.gdc.cancer.gov/) databases. Three populations of TIICs, including CD66b+ tumor-associated neutrophils (TANs), FoxP3+ Tregs, and CD163+ tumor-associated macrophages (TAMs) were selected for immunohistochemistry (IHC) validation analysis in 1,008 CRC biopsies, and their influence on clinical features and prognosis of CRC patients was analyzed. Prognostic models were constructed based on the training cohort (359 patients). The models were further tested and verified in testing (249 patients) and validation cohorts (400 patients). Based on ssGSEA and CIBERSORT analysis, the correlation between TIICs and CRC prognosis was inconsistent in different datasets. Moreover, the results with disease-free survival (DFS) and overall survival (OS) data in the same dataset also differed. The high abundance of TIICs found by ssGSEA or CIBERSORT tools can be used for prognostic evaluation effectively. IHC results showed that TANs, Tregs, TAMs were significantly correlated with prognosis in CRC patients and were independent prognostic factors (PDFS ≤ 0.001; POS ≤ 0.023). The prognostic predictive models were constructed based on the numbers of TANs, Tregs, TAMs (C-indexDFS&OS = 0.86; AICDFS = 448.43; AICOS = 184.30) and they were more reliable than traditional indicators for evaluating prognosis in CRC patients. Besides, TIICs may affect the response to chemotherapy. In conclusion, TIICs were correlated with clinical features and prognosis in patients with CRC and thus can be used as markers.
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spelling doaj.art-9a31fd3b9e92466c91bb6298aec1d6d72022-12-21T21:11:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02368473321Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal CancerLele Ye0Lele Ye1Teming Zhang2Zhengchun Kang3Gangqiang Guo4Yongji Sun5Kangming Lin6Qunjia Huang7Xinyu Shi8Zhonglin Ni9Ning Ding10Kong-Nan Zhao11Wenjun Chang12Junjie Wang13Feng Lin14Xiangyang Xue15Department of Gynecologic Oncology, Wenzhou Central Hospital, Wenzhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Colorectal Surgery, Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, ChinaFirst Clinical College, Wenzhou Medical University, Wenzhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, ChinaDepartment of General Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, ChinaDepartment of Environmental Health, Naval Medical University, Shanghai, ChinaDepartment of Critical Care Medicine, Shanghai Tenth People's Hosptial, Tongji University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Taizhou First People's Hospital, Taizhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, ChinaTumor-infiltrating immune cells (TIICs) play essential roles in cancer development and progression. However, the association of TIICs with prognosis in colorectal cancer (CRC) patients remains elusive. Infiltration of TIICs was assessed using ssGSEA and CIBERSORT tools. The association of TIICs with prognosis was analyzed in 1,802 CRC data downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) and TCGA (https://portal.gdc.cancer.gov/) databases. Three populations of TIICs, including CD66b+ tumor-associated neutrophils (TANs), FoxP3+ Tregs, and CD163+ tumor-associated macrophages (TAMs) were selected for immunohistochemistry (IHC) validation analysis in 1,008 CRC biopsies, and their influence on clinical features and prognosis of CRC patients was analyzed. Prognostic models were constructed based on the training cohort (359 patients). The models were further tested and verified in testing (249 patients) and validation cohorts (400 patients). Based on ssGSEA and CIBERSORT analysis, the correlation between TIICs and CRC prognosis was inconsistent in different datasets. Moreover, the results with disease-free survival (DFS) and overall survival (OS) data in the same dataset also differed. The high abundance of TIICs found by ssGSEA or CIBERSORT tools can be used for prognostic evaluation effectively. IHC results showed that TANs, Tregs, TAMs were significantly correlated with prognosis in CRC patients and were independent prognostic factors (PDFS ≤ 0.001; POS ≤ 0.023). The prognostic predictive models were constructed based on the numbers of TANs, Tregs, TAMs (C-indexDFS&OS = 0.86; AICDFS = 448.43; AICOS = 184.30) and they were more reliable than traditional indicators for evaluating prognosis in CRC patients. Besides, TIICs may affect the response to chemotherapy. In conclusion, TIICs were correlated with clinical features and prognosis in patients with CRC and thus can be used as markers.https://www.frontiersin.org/article/10.3389/fimmu.2019.02368/fullcolorectal cancerTIICsTANsTregsTAMsprognosis
spellingShingle Lele Ye
Lele Ye
Teming Zhang
Zhengchun Kang
Gangqiang Guo
Yongji Sun
Kangming Lin
Qunjia Huang
Xinyu Shi
Zhonglin Ni
Ning Ding
Kong-Nan Zhao
Wenjun Chang
Junjie Wang
Feng Lin
Xiangyang Xue
Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer
Frontiers in Immunology
colorectal cancer
TIICs
TANs
Tregs
TAMs
prognosis
title Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer
title_full Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer
title_fullStr Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer
title_full_unstemmed Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer
title_short Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer
title_sort tumor infiltrating immune cells act as a marker for prognosis in colorectal cancer
topic colorectal cancer
TIICs
TANs
Tregs
TAMs
prognosis
url https://www.frontiersin.org/article/10.3389/fimmu.2019.02368/full
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