Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma

被引：2

作者：

Xiao, Yiwei ^{[1
,2
]}

Cao, Junning ^{[3
]}

Zhang, Ze ^{[3
]}

Zeng, Chaoting ^{[3
]}

Ou, Guomin ^{[1
,2
]}

Shi, Jihang ^{[3
]}

Liu, Zhixiu ^{[1
,2
,4
]}

Li, Yi ^{[1
,2
]}

Deng, Juan ^{[1
,2
]}

Xu, Yinzhe ^{[3
]}

Zhang, Wenwen ^{[3
]}

Li, Jie ^{[1
,2
]}

Li, Tong ^{[1
,2
,5
]}

Zhuang, Hui ^{[1
,2
,5
]}

Lu, Shichun ^{[3
]}

Xiang, Kuanhui ^{[1
,2
,5
]}

机构：

[1] Peking Univ, Dept Microbiol, Sch Basic Med Sci, Hlth Sci Ctr, Beijing, Peoples R China

[2] Peking Univ, Infect Dis Ctr, Sch Basic Med Sci, Hlth Sci Ctr, Beijing, Peoples R China

[3] Chinese PLA Genera Hosp, Fac Hepatopancreatobiliary Surg, Beijing, Peoples R China

[4] Hebei Yanda Lu Daopei Hosp, Div Pathol & Lab Med, Langfang, Peoples R China

[5] Peking Univ, Peking Univ YHLO Joint Lab Mol Diagnost Infect Di, Beijing, Peoples R China

来源：

FRONTIERS IN MICROBIOLOGY | 2022年 / 13卷

基金：

中国国家自然科学基金;

关键词：

hepatitis B virus; viral replication; pgRNA; hepatocellular carcinoma; cancer stem cell; HUMAN HEPATOCYTES; APPEARANCE; SIGNATURE; BURDEN; DEATH;

D O I：

10.3389/fmicb.2022.830741

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

BackgroundThe existence of hepatic cancer stem cells (CSCs) contributes to chemotherapy resistance and cancer recurrence after treatment or surgery. However, very little is known about the hepatitis B virus (HBV) replication and its relationship with the stemness of hepatocellular carcinoma (HCC) in HBV-related HCC patients. MethodsWe collected tumor tissues (T), matched adjacent non-tumor tissues (NT), and distal non-tumor tissues (FNT) from 55 HCC patients for analysis. ResultsWe found HBV DNA levels were higher in T samples than NT and FNT samples, but HBV pgRNA and total RNA expressed lower in T samples. HBV pgRNA and total RNA correlate to HBV DNA among the T, NT, and FNT samples. Further evidence for HBV replication in T samples was provided by HBV S, reverse transcriptase, and X genes sequencing, showing that HBV sequences and genotypes differed between T and matched NT and FNT samples. HBV pgRNA and total RNA showed more frequent significant correlations with CSC markers in NT samples in HBsAg-positive patients. The markers CD133 and OCT4 expressed higher in FNT samples, and HBV replication marker of pgRNA levels was significantly positively correlated to these two markers only in FNT samples. The detection of pgRNA and OCT4 in FNT was correlated to the recurrence of HCC in the resection of HCC patients. Analysis of HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP), showed that NTCP was correlated negatively to CSC markers in T samples, except for the CD44. ConclusionHBV replication may present in HCC with a weak transcriptomic signature. Moreover, the expression level of HBV pgRNA in distal non-tumor tissues is a sensitive marker for HBV replication and prognosis, which is associated with CSC-related markers especially with OCT4 in distal non-tumor tissues and recurrence of HCC in HBV-related HCC patients.

引用

页数：13

共 31 条

[31] Single-cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma [J].

Zheng, Hongping ;

Pomyen, Yotsawat ;

Hernandez, Maria Olga ;

Li, Caiyi ;

Livak, Ferenc ;

Tang, Wei ;

Dang, Hien ;

Greten, Tim F. ;

Davis, Jeremy L. ;

Zhao, Yongmei ;

Mehta, Monika ;

Levin, Yelena ;

Shetty, Jyoti ;

Tran, Bao ;

Budhu, Anuradha ;

Wang, Xin Wei .

HEPATOLOGY, 2018, 68 (01) :127-140

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