Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer. The lack of prognosis indicators is one of the challenges in HCC. In this study, we investigated the combination of tertiary lymphoid structure (TLS) and several systemic inflammation parameters as...

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Main Authors: Shaodi Wen, Yuzhong Chen, Chupeng Hu, Xiaoyue Du, Jingwei Xia, Xin Wang, Wei Zhu, Qingbo Wang, Miaolin Zhu, Yun Chen, Bo Shen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.788640/full
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author Shaodi Wen
Yuzhong Chen
Chupeng Hu
Xiaoyue Du
Jingwei Xia
Xin Wang
Wei Zhu
Qingbo Wang
Miaolin Zhu
Yun Chen
Yun Chen
Yun Chen
Bo Shen
author_facet Shaodi Wen
Yuzhong Chen
Chupeng Hu
Xiaoyue Du
Jingwei Xia
Xin Wang
Wei Zhu
Qingbo Wang
Miaolin Zhu
Yun Chen
Yun Chen
Yun Chen
Bo Shen
author_sort Shaodi Wen
collection DOAJ
description BackgroundHepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer. The lack of prognosis indicators is one of the challenges in HCC. In this study, we investigated the combination of tertiary lymphoid structure (TLS) and several systemic inflammation parameters as a prognosis indicator for HCC.Materials and MethodsWe retrospectively recruited 126 postoperative patients with primary HCC. The paraffin section was collected for TLS density assessment. In addition, we collected the systemic inflammation parameters from peripheral blood samples. We evaluated the prognostic values of those parameters on overall survival (OS) using Kaplan-Meier curves, univariate and multivariate Cox regression. Last, we plotted a nomogram to predict the survival of HCC patients.ResultsWe first found TLS density was positively correlated with HCC patients’ survival (HR=0.16, 95% CI: 0.06 − 0.39, p < 0.0001), but the power of TLS density for survival prediction was found to be limited (AUC=0.776, 95% CI:0.772 − 0.806). Thus, we further introduced several systemic inflammation parameters for survival analysis, we found neutrophil-to-lymphocyte ratio (NLR) was positively associated with OS in univariate Cox regression analysis. However, the combination of TLS density and NLR better predicts patient’s survival (AUC=0.800, 95% CI: 0.698-0.902, p < 0.001) compared with using any single indicator alone. Last, we incorporated TLS density, NLR, and other parameters into the nomogram to provide a reproducible approach for survival prediction in HCC clinical practice.ConclusionThe combination of TLS density and NLR was shown to be a good predictor of HCC patient survival. It also provides a novel direction for the evaluation of immunotherapies in HCC.
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spelling doaj.art-84eee63a27a54261b27e3aaa3c7d5aba2022-12-22T04:12:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.788640788640Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular CarcinomaShaodi Wen0Yuzhong Chen1Chupeng Hu2Xiaoyue Du3Jingwei Xia4Xin Wang5Wei Zhu6Qingbo Wang7Miaolin Zhu8Yun Chen9Yun Chen10Yun Chen11Bo Shen12The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaKey Laboratory of Microenvironment and Major Diseases, Department of Immunology, Nanjing Medical University, Nanjing, ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, ChinaDepartment of Chemotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaKey Laboratory of Microenvironment and Major Diseases, Department of Immunology, Nanjing Medical University, Nanjing, ChinaJiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaBackgroundHepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer. The lack of prognosis indicators is one of the challenges in HCC. In this study, we investigated the combination of tertiary lymphoid structure (TLS) and several systemic inflammation parameters as a prognosis indicator for HCC.Materials and MethodsWe retrospectively recruited 126 postoperative patients with primary HCC. The paraffin section was collected for TLS density assessment. In addition, we collected the systemic inflammation parameters from peripheral blood samples. We evaluated the prognostic values of those parameters on overall survival (OS) using Kaplan-Meier curves, univariate and multivariate Cox regression. Last, we plotted a nomogram to predict the survival of HCC patients.ResultsWe first found TLS density was positively correlated with HCC patients’ survival (HR=0.16, 95% CI: 0.06 − 0.39, p < 0.0001), but the power of TLS density for survival prediction was found to be limited (AUC=0.776, 95% CI:0.772 − 0.806). Thus, we further introduced several systemic inflammation parameters for survival analysis, we found neutrophil-to-lymphocyte ratio (NLR) was positively associated with OS in univariate Cox regression analysis. However, the combination of TLS density and NLR better predicts patient’s survival (AUC=0.800, 95% CI: 0.698-0.902, p < 0.001) compared with using any single indicator alone. Last, we incorporated TLS density, NLR, and other parameters into the nomogram to provide a reproducible approach for survival prediction in HCC clinical practice.ConclusionThe combination of TLS density and NLR was shown to be a good predictor of HCC patient survival. It also provides a novel direction for the evaluation of immunotherapies in HCC.https://www.frontiersin.org/articles/10.3389/fimmu.2021.788640/fullhepatocellular carcinomatertiary lymphoid structureneutrophil-to-lymphocyte ratio (NLR)overall survivalinflammation
spellingShingle Shaodi Wen
Yuzhong Chen
Chupeng Hu
Xiaoyue Du
Jingwei Xia
Xin Wang
Wei Zhu
Qingbo Wang
Miaolin Zhu
Yun Chen
Yun Chen
Yun Chen
Bo Shen
Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma
Frontiers in Immunology
hepatocellular carcinoma
tertiary lymphoid structure
neutrophil-to-lymphocyte ratio (NLR)
overall survival
inflammation
title Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma
title_full Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma
title_fullStr Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma
title_full_unstemmed Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma
title_short Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma
title_sort combination of tertiary lymphoid structure and neutrophil to lymphocyte ratio predicts survival in patients with hepatocellular carcinoma
topic hepatocellular carcinoma
tertiary lymphoid structure
neutrophil-to-lymphocyte ratio (NLR)
overall survival
inflammation
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.788640/full
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