Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation
Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samp...
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Published in | NPJ precision oncology Vol. 5; no. 1; p. 27 |
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Language | English |
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26.03.2021
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Abstract | Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samples from a Korean HCC cohort in which 38 patients underwent total hepatectomy, as well as for 15 normal and 47 adjacent nontumor samples. Using in silico deconvolution of expression mixtures, 22 immune cell fractions for each sample were inferred, and validated with immune cell counting by immunohistochemistry. Cell type-specific immune signatures dynamically shifted from premalignant stages to the late HCC stage. Total hepatectomy patients displayed elevated immune infiltration and prolonged disease-free survival compared to the partial hepatectomy patients. However, patients who exhibited an infiltration of regulatory T cells (Tregs) during the pretransplantation period displayed a high risk of tumor relapse with suppressed immune responses, and pretreatment was a potential driver of Treg infiltration in the total hepatectomy group. Treg infiltration appeared to be independent of molecular classifications based on transcriptomic data. Our study provides not only comprehensive immune signatures in adjacent nontumor lesions and early malignant HCC stages but also clinical guidance for HCC patients who will undergo liver transplantation. |
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AbstractList | Abstract Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samples from a Korean HCC cohort in which 38 patients underwent total hepatectomy, as well as for 15 normal and 47 adjacent nontumor samples. Using in silico deconvolution of expression mixtures, 22 immune cell fractions for each sample were inferred, and validated with immune cell counting by immunohistochemistry. Cell type-specific immune signatures dynamically shifted from premalignant stages to the late HCC stage. Total hepatectomy patients displayed elevated immune infiltration and prolonged disease-free survival compared to the partial hepatectomy patients. However, patients who exhibited an infiltration of regulatory T cells (Tregs) during the pretransplantation period displayed a high risk of tumor relapse with suppressed immune responses, and pretreatment was a potential driver of Treg infiltration in the total hepatectomy group. Treg infiltration appeared to be independent of molecular classifications based on transcriptomic data. Our study provides not only comprehensive immune signatures in adjacent nontumor lesions and early malignant HCC stages but also clinical guidance for HCC patients who will undergo liver transplantation. Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samples from a Korean HCC cohort in which 38 patients underwent total hepatectomy, as well as for 15 normal and 47 adjacent nontumor samples. Using in silico deconvolution of expression mixtures, 22 immune cell fractions for each sample were inferred, and validated with immune cell counting by immunohistochemistry. Cell type-specific immune signatures dynamically shifted from premalignant stages to the late HCC stage. Total hepatectomy patients displayed elevated immune infiltration and prolonged disease-free survival compared to the partial hepatectomy patients. However, patients who exhibited an infiltration of regulatory T cells (Tregs) during the pretransplantation period displayed a high risk of tumor relapse with suppressed immune responses, and pretreatment was a potential driver of Treg infiltration in the total hepatectomy group. Treg infiltration appeared to be independent of molecular classifications based on transcriptomic data. Our study provides not only comprehensive immune signatures in adjacent nontumor lesions and early malignant HCC stages but also clinical guidance for HCC patients who will undergo liver transplantation. |
ArticleNumber | 27 |
Author | Yoon, Sang-Ho Choi, Seo-Won Nam, Jin-Wu Lee, Kyoung Bun Nam, Suk Woo |
Author_xml | – sequence: 1 givenname: Sang-Ho orcidid: 0000-0003-2611-5554 surname: Yoon fullname: Yoon, Sang-Ho organization: Department of Life Science, College of Natural Sciences, Hanyang University – sequence: 2 givenname: Seo-Won surname: Choi fullname: Choi, Seo-Won organization: Department of Life Science, College of Natural Sciences, Hanyang University – sequence: 3 givenname: Suk Woo surname: Nam fullname: Nam, Suk Woo organization: Department of Pathology, College of Medicine, The Catholic University of Korea – sequence: 4 givenname: Kyoung Bun surname: Lee fullname: Lee, Kyoung Bun email: kblee@snuh.org organization: Department of Pathology, College of Medicine, Seoul National University – sequence: 5 givenname: Jin-Wu orcidid: 0000-0003-0047-3687 surname: Nam fullname: Nam, Jin-Wu email: jwnam@hanyang.ac.kr organization: Department of Life Science, College of Natural Sciences, Hanyang University, Research Institute for Convergence of Basic Sciences, Hanyang University, Research Institute for Natural Sciences, Hanyang University |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33772139$$D View this record in MEDLINE/PubMed |
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Snippet | Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and... Abstract Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in... |
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SubjectTerms | 631/67/1504/1610/4029 631/67/1857 631/67/327 Cancer Research Clinical outcomes Gene expression Gene Therapy Hepatitis Human Genetics Immunotherapy Internal Medicine Liver cancer Liver transplants Lymphocytes Medicine Medicine & Public Health Metabolism Oncology Principal components analysis Proteins Targeted cancer therapy Tumors Viral infections |
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Title | Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation |
URI | https://link.springer.com/article/10.1038/s41698-021-00167-2 https://www.ncbi.nlm.nih.gov/pubmed/33772139 https://www.proquest.com/docview/2505572268 https://search.proquest.com/docview/2506276235 https://pubmed.ncbi.nlm.nih.gov/PMC7997876 https://doaj.org/article/be2d57dbb8d94979ae11c1777d38e809 |
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