Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved
<b>Background:</b> We investigated whether the degree of inflammation and fibrosis in para-carcinoma tissue can predict prognosis of patients with non-cirrhotic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after hepatectomy. We also explored the mechanisms through wh...
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MDPI AG
2022-12-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/30/1/16 |
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| author | Yan Li Jing-Fei Zhao Jie Zhang Guo-Hua Zhan Yuan-Kuan Li Jun-Tao Huang Xi Huang Bang-De Xiang |
| author_facet | Yan Li Jing-Fei Zhao Jie Zhang Guo-Hua Zhan Yuan-Kuan Li Jun-Tao Huang Xi Huang Bang-De Xiang |
| author_sort | Yan Li |
| collection | DOAJ |
| description | <b>Background:</b> We investigated whether the degree of inflammation and fibrosis in para-carcinoma tissue can predict prognosis of patients with non-cirrhotic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after hepatectomy. We also explored the mechanisms through which inflammation and fibrosis might affect prognosis. <b>Methods:</b> Clinicopathological data were retrospectively analyzed from 293 patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2012 to 2017. Based on the Scheuer score system, patients were classified into those showing mild or moderate-to-severe inflammation and fibrosis. Rates of overall and recurrence-free survival were compared between the groups using Kaplan–Meier curves, and survival predictors were identified using Cox regression. Using tumor and para-tumor tissues from independent samples of patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2018 to 2019, we performed next-generation sequencing and time-of-flight cytometry (CyTOF) to examine the influence of inflammation and fibrosis on gene expression and immune cell infiltration. <b>Results:</b> In the analysis of the 293 patients, those with mild inflammation and fibrosis showed significantly better overall and recurrence-free survival than those with moderate-to-severe inflammation and fibrosis. Multivariate Cox regression confirmed that moderate-to-severe inflammation and fibrosis were independent risk factors for worse survival. RNA sequencing and CyTOF showed that more severe inflammation and fibrosis were associated with stronger invasion and migration by hepatocytes. In cancerous tissues, the biological processes of cell proliferation were upregulated, the signaling pathways promoting tumor growth were activated, the proportion of Th17 cells promoting tumor progression was increased, and CD8+ T cells expressed higher levels of PD-L1. In para-cancerous tissues, biological processes of immune response and cell chemotaxis were downregulated, and the proportion of tumor-killing immune cells was decreased. <b>Conclusion:</b> Worse inflammation and fibrosis in non-cirrhotic HBV-associated HCC is associated with worse prognosis, which may reflect more aggressive tumor behavior and an immunosuppressed, pro-metastatic tumor microenvironment. |
| first_indexed | 2024-03-09T13:06:01Z |
| format | Article |
| id | doaj.art-bbcbb8f1efda416a834dc0778c85a9ec |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-09T13:06:01Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | Current Oncology |
| spelling | doaj.art-bbcbb8f1efda416a834dc0778c85a9ec2023-11-30T21:49:01ZengMDPI AGCurrent Oncology1198-00521718-77292022-12-0130119621810.3390/curroncol30010016Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms InvolvedYan Li0Jing-Fei Zhao1Jie Zhang2Guo-Hua Zhan3Yuan-Kuan Li4Jun-Tao Huang5Xi Huang6Bang-De Xiang7Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, ChinaDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, ChinaDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, ChinaDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, ChinaDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, ChinaDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, ChinaThe First Clinical School of Guangxi Medical University, Nanning 530021, ChinaDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China<b>Background:</b> We investigated whether the degree of inflammation and fibrosis in para-carcinoma tissue can predict prognosis of patients with non-cirrhotic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after hepatectomy. We also explored the mechanisms through which inflammation and fibrosis might affect prognosis. <b>Methods:</b> Clinicopathological data were retrospectively analyzed from 293 patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2012 to 2017. Based on the Scheuer score system, patients were classified into those showing mild or moderate-to-severe inflammation and fibrosis. Rates of overall and recurrence-free survival were compared between the groups using Kaplan–Meier curves, and survival predictors were identified using Cox regression. Using tumor and para-tumor tissues from independent samples of patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2018 to 2019, we performed next-generation sequencing and time-of-flight cytometry (CyTOF) to examine the influence of inflammation and fibrosis on gene expression and immune cell infiltration. <b>Results:</b> In the analysis of the 293 patients, those with mild inflammation and fibrosis showed significantly better overall and recurrence-free survival than those with moderate-to-severe inflammation and fibrosis. Multivariate Cox regression confirmed that moderate-to-severe inflammation and fibrosis were independent risk factors for worse survival. RNA sequencing and CyTOF showed that more severe inflammation and fibrosis were associated with stronger invasion and migration by hepatocytes. In cancerous tissues, the biological processes of cell proliferation were upregulated, the signaling pathways promoting tumor growth were activated, the proportion of Th17 cells promoting tumor progression was increased, and CD8+ T cells expressed higher levels of PD-L1. In para-cancerous tissues, biological processes of immune response and cell chemotaxis were downregulated, and the proportion of tumor-killing immune cells was decreased. <b>Conclusion:</b> Worse inflammation and fibrosis in non-cirrhotic HBV-associated HCC is associated with worse prognosis, which may reflect more aggressive tumor behavior and an immunosuppressed, pro-metastatic tumor microenvironment.https://www.mdpi.com/1718-7729/30/1/16inflammationfibrosishepatocellular carcinomahepatitis B virusRNA sequencingCyTOF |
| spellingShingle | Yan Li Jing-Fei Zhao Jie Zhang Guo-Hua Zhan Yuan-Kuan Li Jun-Tao Huang Xi Huang Bang-De Xiang Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved Current Oncology inflammation fibrosis hepatocellular carcinoma hepatitis B virus RNA sequencing CyTOF |
| title | Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved |
| title_full | Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved |
| title_fullStr | Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved |
| title_full_unstemmed | Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved |
| title_short | Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved |
| title_sort | inflammation and fibrosis in patients with non cirrhotic hepatitis b virus associated hepatocellular carcinoma impact on prognosis after hepatectomy and mechanisms involved |
| topic | inflammation fibrosis hepatocellular carcinoma hepatitis B virus RNA sequencing CyTOF |
| url | https://www.mdpi.com/1718-7729/30/1/16 |
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