Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C.
Circulating microRNAs have been widely recognized as a novel category of biomarker in a variety of physiological and pathological conditions. Other reports revealed that fragments of organ specific messenger RNAs are also detectable in serum/plasma and can be utilized as sensitive indicators of live...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3958472?pdf=render |
| _version_ | 1818137935790211072 |
|---|---|
| author | Xiaonan Zhang Zhanqing Zhang Fahui Dai Bisheng Shi Liang Chen Xinxin Zhang Guoqing Zang Jiming Zhang Xiaorong Chen Fangxing Qian Yunwen Hu Zhenghong Yuan |
| author_facet | Xiaonan Zhang Zhanqing Zhang Fahui Dai Bisheng Shi Liang Chen Xinxin Zhang Guoqing Zang Jiming Zhang Xiaorong Chen Fangxing Qian Yunwen Hu Zhenghong Yuan |
| author_sort | Xiaonan Zhang |
| collection | DOAJ |
| description | Circulating microRNAs have been widely recognized as a novel category of biomarker in a variety of physiological and pathological conditions. Other reports revealed that fragments of organ specific messenger RNAs are also detectable in serum/plasma and can be utilized as sensitive indicators of liver pathology and cancer. In order to assess the sensitivity and reliability of these two class of RNAs as marker of hepatitis B or C induced chronic liver disease, we collected plasma samples from 156 chronic hepatitis B or C patients (HBV active n = 112, HBV carrier n = 19, hepatitis C n = 25) and 22 healthy donors and quantified their circulating mRNA for albumin, HP (haptoglobin), CYP2E1 (cytochrome P450, family 2, subfamily E) and ApoA2 (Apolipoprotein A2) in conjunction with microRNA-122, a well established marker for acute and chronic liver injury. We found that plasma microRNA-122 level is significantly elevated in patients with active HBV but not in HBV carriers. Furthermore, microRNA-122 is not elevated in HCV patients even though their median serum alanine aminotransferase (sALT) was three fold of the healthy donors. Nevertheless, circulating mRNAs, especially albumin mRNA, showed much more sensitivity in distinguishing active hepatitis B, hepatitis B carrier or HCV patients from healthy control. Correlation and multiple linear regression analysis suggested that circulating mRNAs and miRNAs are much more related to HBsAg titre than to sALT. Immunoprecipitation of HBsAg in HBV patients' plasma resulted in enrichment of albumin and HP mRNA suggesting that fragments of liver specific transcripts can be encapsidated into HBsAg particles. Taken together, our results suggest that hepatocyte specific transcripts in plasma like albumin mRNA showed greater sensitivity and specificity in differentiating HBV or HCV induced chronic liver disease than microRNA-122. Circulating mRNA fragments merit more attention in the quest of next generation biomarkers for various maladies. |
| first_indexed | 2024-12-11T10:04:13Z |
| format | Article |
| id | doaj.art-6c58716bdd8744de855df6a8704c5121 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T10:04:13Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6c58716bdd8744de855df6a8704c51212022-12-22T01:12:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9211210.1371/journal.pone.0092112Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C.Xiaonan ZhangZhanqing ZhangFahui DaiBisheng ShiLiang ChenXinxin ZhangGuoqing ZangJiming ZhangXiaorong ChenFangxing QianYunwen HuZhenghong YuanCirculating microRNAs have been widely recognized as a novel category of biomarker in a variety of physiological and pathological conditions. Other reports revealed that fragments of organ specific messenger RNAs are also detectable in serum/plasma and can be utilized as sensitive indicators of liver pathology and cancer. In order to assess the sensitivity and reliability of these two class of RNAs as marker of hepatitis B or C induced chronic liver disease, we collected plasma samples from 156 chronic hepatitis B or C patients (HBV active n = 112, HBV carrier n = 19, hepatitis C n = 25) and 22 healthy donors and quantified their circulating mRNA for albumin, HP (haptoglobin), CYP2E1 (cytochrome P450, family 2, subfamily E) and ApoA2 (Apolipoprotein A2) in conjunction with microRNA-122, a well established marker for acute and chronic liver injury. We found that plasma microRNA-122 level is significantly elevated in patients with active HBV but not in HBV carriers. Furthermore, microRNA-122 is not elevated in HCV patients even though their median serum alanine aminotransferase (sALT) was three fold of the healthy donors. Nevertheless, circulating mRNAs, especially albumin mRNA, showed much more sensitivity in distinguishing active hepatitis B, hepatitis B carrier or HCV patients from healthy control. Correlation and multiple linear regression analysis suggested that circulating mRNAs and miRNAs are much more related to HBsAg titre than to sALT. Immunoprecipitation of HBsAg in HBV patients' plasma resulted in enrichment of albumin and HP mRNA suggesting that fragments of liver specific transcripts can be encapsidated into HBsAg particles. Taken together, our results suggest that hepatocyte specific transcripts in plasma like albumin mRNA showed greater sensitivity and specificity in differentiating HBV or HCV induced chronic liver disease than microRNA-122. Circulating mRNA fragments merit more attention in the quest of next generation biomarkers for various maladies.http://europepmc.org/articles/PMC3958472?pdf=render |
| spellingShingle | Xiaonan Zhang Zhanqing Zhang Fahui Dai Bisheng Shi Liang Chen Xinxin Zhang Guoqing Zang Jiming Zhang Xiaorong Chen Fangxing Qian Yunwen Hu Zhenghong Yuan Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C. PLoS ONE |
| title | Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C. |
| title_full | Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C. |
| title_fullStr | Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C. |
| title_full_unstemmed | Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C. |
| title_short | Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C. |
| title_sort | comparison of circulating hepatocyte specific messenger rna and microrna as biomarkers for chronic hepatitis b and c |
| url | http://europepmc.org/articles/PMC3958472?pdf=render |
| work_keys_str_mv | AT xiaonanzhang comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT zhanqingzhang comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT fahuidai comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT bishengshi comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT liangchen comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT xinxinzhang comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT guoqingzang comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT jimingzhang comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT xiaorongchen comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT fangxingqian comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT yunwenhu comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc AT zhenghongyuan comparisonofcirculatinghepatocytespecificmessengerrnaandmicrornaasbiomarkersforchronichepatitisbandc |