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...

Full description

Bibliographic Details
Main Authors: Ruizhi Wang, Yichao Zhu, Hao Zhong, Xinyue Gao, Qiang Sun, Meifang He
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1007305/full
_version_ 1828311655070564352
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.
first_indexed 2024-04-13T16:02:47Z
format Article
id doaj.art-29e1a55cfbbd40bcafc5468a9bc74e08
institution Directory Open Access Journal
issn 2234-943X
language English
last_indexed 2024-04-13T16:02:47Z
publishDate 2022-11-01
publisher Frontiers Media S.A.
record_format Article
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
work_keys_str_mv AT ruizhiwang homotypiccellincellstructuresasanadverseprognosticpredictorofhepatocellularcarcinoma
AT ruizhiwang homotypiccellincellstructuresasanadverseprognosticpredictorofhepatocellularcarcinoma
AT yichaozhu homotypiccellincellstructuresasanadverseprognosticpredictorofhepatocellularcarcinoma
AT haozhong homotypiccellincellstructuresasanadverseprognosticpredictorofhepatocellularcarcinoma
AT xinyuegao homotypiccellincellstructuresasanadverseprognosticpredictorofhepatocellularcarcinoma
AT qiangsun homotypiccellincellstructuresasanadverseprognosticpredictorofhepatocellularcarcinoma
AT meifanghe homotypiccellincellstructuresasanadverseprognosticpredictorofhepatocellularcarcinoma