Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis
There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline conte...
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MDPI AG
2020-10-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/10/10/784 |
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| author | Tyler L. Bissoondial Yiguang Han Stephanie Mullan Amrit K. Pabla Kiera Spahn Steven Shi Lana Zheng Ping Zhou Kai Jiang Natalia Prakash Shraddha Bhutkar Quaisar Ali Jingsong Li Zhijian Hu Anthony J. Pellicano Itzhak D. Goldberg Prakash Narayan |
| author_facet | Tyler L. Bissoondial Yiguang Han Stephanie Mullan Amrit K. Pabla Kiera Spahn Steven Shi Lana Zheng Ping Zhou Kai Jiang Natalia Prakash Shraddha Bhutkar Quaisar Ali Jingsong Li Zhijian Hu Anthony J. Pellicano Itzhak D. Goldberg Prakash Narayan |
| author_sort | Tyler L. Bissoondial |
| collection | DOAJ |
| description | There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content of liver biopsy samples is diagnostic for HCC in murine models of NASH induced by diet or by diet and chemicals. The training set comprised mice fed a standard diet or a fast-food diet with or without administration of thioacetamide. At harvest, livers from the modified diet cohort exhibited NASH with a subset of NASH livers exhibiting HCC. Hydroxyproline content was measured in liver biopsy samples with tissue in the NASH+HCC cohort sampled from the remote, nontumor parenchyma. Plotting the receiver operating characteristics (ROC) with hydroxyproline as the continuous variable against the absence or presence of HCC yielded an area under ROC of 0.87, a threshold of >0.18 μg hydroxyproline/mg liver and sensitivity of 91% with a specificity of 83.3%. The use of liver hydroxyproline content as a diagnostic for HCC in a test set comprising healthy, NASH and NASH+HCC livers proved 87% accurate. |
| first_indexed | 2024-03-10T15:50:22Z |
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| id | doaj.art-135af65593844de493e4173d5d75c0ff |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T15:50:22Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-135af65593844de493e4173d5d75c0ff2023-11-20T16:03:54ZengMDPI AGDiagnostics2075-44182020-10-01101078410.3390/diagnostics10100784Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic SteatohepatitisTyler L. Bissoondial0Yiguang Han1Stephanie Mullan2Amrit K. Pabla3Kiera Spahn4Steven Shi5Lana Zheng6Ping Zhou7Kai Jiang8Natalia Prakash9Shraddha Bhutkar10Quaisar Ali11Jingsong Li12Zhijian Hu13Anthony J. Pellicano14Itzhak D. Goldberg15Prakash Narayan16Department of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USAThere is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content of liver biopsy samples is diagnostic for HCC in murine models of NASH induced by diet or by diet and chemicals. The training set comprised mice fed a standard diet or a fast-food diet with or without administration of thioacetamide. At harvest, livers from the modified diet cohort exhibited NASH with a subset of NASH livers exhibiting HCC. Hydroxyproline content was measured in liver biopsy samples with tissue in the NASH+HCC cohort sampled from the remote, nontumor parenchyma. Plotting the receiver operating characteristics (ROC) with hydroxyproline as the continuous variable against the absence or presence of HCC yielded an area under ROC of 0.87, a threshold of >0.18 μg hydroxyproline/mg liver and sensitivity of 91% with a specificity of 83.3%. The use of liver hydroxyproline content as a diagnostic for HCC in a test set comprising healthy, NASH and NASH+HCC livers proved 87% accurate.https://www.mdpi.com/2075-4418/10/10/784NASHfattynonalcoholicliverHCCcancer |
| spellingShingle | Tyler L. Bissoondial Yiguang Han Stephanie Mullan Amrit K. Pabla Kiera Spahn Steven Shi Lana Zheng Ping Zhou Kai Jiang Natalia Prakash Shraddha Bhutkar Quaisar Ali Jingsong Li Zhijian Hu Anthony J. Pellicano Itzhak D. Goldberg Prakash Narayan Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis Diagnostics NASH fatty nonalcoholic liver HCC cancer |
| title | Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis |
| title_full | Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis |
| title_fullStr | Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis |
| title_full_unstemmed | Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis |
| title_short | Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis |
| title_sort | liver biopsy hydroxyproline content is a diagnostic for hepatocellular carcinoma in murine models of nonalcoholic steatohepatitis |
| topic | NASH fatty nonalcoholic liver HCC cancer |
| url | https://www.mdpi.com/2075-4418/10/10/784 |
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