Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors. A homotypic cell-in-cell structure (hoCIC) refers to one or more cells internalized into the same type as their neighbors, which predominantly occurs in multiple tumors. The objective of this study was to investigate th...
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Frontiers Media S.A.
2022-11-01
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Series: | Frontiers in Oncology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1007305/full |
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author | Ruizhi Wang Ruizhi Wang Yichao Zhu Hao Zhong Xinyue Gao Qiang Sun Meifang He |
author_facet | Ruizhi Wang Ruizhi Wang Yichao Zhu Hao Zhong Xinyue Gao Qiang Sun Meifang He |
author_sort | Ruizhi Wang |
collection | DOAJ |
description | Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors. A homotypic cell-in-cell structure (hoCIC) refers to one or more cells internalized into the same type as their neighbors, which predominantly occurs in multiple tumors. The objective of this study was to investigate the prognostic value of hoCICs in HCC and its relationship with other clinicopathological features. By immunostaining analysis of a panel of HCC tissues, we found that hoCICs were prevalent in tumor tissues (54/90) but not in para-tumor tissues (17/90). The presence of hoCICs in tumor tissues was closely associated with E-cadherin expression. The presence of CICs was identified as significantly associated with poor survival rates of patients with HCC, comparable to traditional clinicopathological parameters, such as histological grade [hazard ratio (HR) = 0.734, p = 0.320]. Multivariate Cox regression analysis further confirmed that CICs were an independent risk factor for poor survival (HR = 1.902, p = 0.047). In addition, hoCICs were the predominant contributor in a nomogram model constructed for survival prediction at 1, 3, and 5 years [the areas under the curve (AUCs) were 0.760, 0.733, and 0.794, respectively]. Stratification analysis indicated that hoCICs tend to selectively affect patients with high-grade disease (HR = 2.477, p = 0.009) and at the early TNM stage (HR = 2.351, p = 0.05). Thus, hoCICs predict poor survival of patients with HCC, particularly those with higher grades and at an early stage. |
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language | English |
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series | Frontiers in Oncology |
spelling | doaj.art-29e1a55cfbbd40bcafc5468a9bc74e082022-12-22T02:40:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10073051007305Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinomaRuizhi Wang0Ruizhi Wang1Yichao Zhu2Hao Zhong3Xinyue Gao4Qiang Sun5Meifang He6Laboratory of General Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaBeijing Institute of Biotechnology; Research Unit of Cell Death Mechanism, Chinese Academy of Medical Science, Beijing, ChinaLaboratory of General Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaBeijing Institute of Biotechnology; Research Unit of Cell Death Mechanism, Chinese Academy of Medical Science, Beijing, ChinaBeijing Institute of Biotechnology; Research Unit of Cell Death Mechanism, Chinese Academy of Medical Science, Beijing, ChinaLaboratory of General Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaHepatocellular carcinoma (HCC) is one of the most common malignant liver tumors. A homotypic cell-in-cell structure (hoCIC) refers to one or more cells internalized into the same type as their neighbors, which predominantly occurs in multiple tumors. The objective of this study was to investigate the prognostic value of hoCICs in HCC and its relationship with other clinicopathological features. By immunostaining analysis of a panel of HCC tissues, we found that hoCICs were prevalent in tumor tissues (54/90) but not in para-tumor tissues (17/90). The presence of hoCICs in tumor tissues was closely associated with E-cadherin expression. The presence of CICs was identified as significantly associated with poor survival rates of patients with HCC, comparable to traditional clinicopathological parameters, such as histological grade [hazard ratio (HR) = 0.734, p = 0.320]. Multivariate Cox regression analysis further confirmed that CICs were an independent risk factor for poor survival (HR = 1.902, p = 0.047). In addition, hoCICs were the predominant contributor in a nomogram model constructed for survival prediction at 1, 3, and 5 years [the areas under the curve (AUCs) were 0.760, 0.733, and 0.794, respectively]. Stratification analysis indicated that hoCICs tend to selectively affect patients with high-grade disease (HR = 2.477, p = 0.009) and at the early TNM stage (HR = 2.351, p = 0.05). Thus, hoCICs predict poor survival of patients with HCC, particularly those with higher grades and at an early stage.https://www.frontiersin.org/articles/10.3389/fonc.2022.1007305/fullhomotypic cell-in-cell structures (hoCICs)E-cadherinprognostic predictoroverall survival (OS)hepatocellular carcinoma (HCC) |
spellingShingle | Ruizhi Wang Ruizhi Wang Yichao Zhu Hao Zhong Xinyue Gao Qiang Sun Meifang He Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma Frontiers in Oncology homotypic cell-in-cell structures (hoCICs) E-cadherin prognostic predictor overall survival (OS) hepatocellular carcinoma (HCC) |
title | Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma |
title_full | Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma |
title_fullStr | Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma |
title_full_unstemmed | Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma |
title_short | Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma |
title_sort | homotypic cell in cell structures as an adverse prognostic predictor of hepatocellular carcinoma |
topic | homotypic cell-in-cell structures (hoCICs) E-cadherin prognostic predictor overall survival (OS) hepatocellular carcinoma (HCC) |
url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1007305/full |
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