HCC: RNA-Sequencing in Cirrhosis

Hepatocellular carcinoma (HCC) ranks the most common types of cancer worldwide. As the fourth leading cause of cancer-related deaths, its prognosis remains poor. Most patients developed HCC on the basis of chronic liver disease. Cirrhosis is an important precancerous lesion for HCC. However, the mol...

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Main Authors: Haoyu Wang, Wenjie Shi, Jing Lu, Yuan Liu, Wei Zhou, Zekun Yu, Shengying Qin, Junwei Fan
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/1/141
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author Haoyu Wang
Wenjie Shi
Jing Lu
Yuan Liu
Wei Zhou
Zekun Yu
Shengying Qin
Junwei Fan
author_facet Haoyu Wang
Wenjie Shi
Jing Lu
Yuan Liu
Wei Zhou
Zekun Yu
Shengying Qin
Junwei Fan
author_sort Haoyu Wang
collection DOAJ
description Hepatocellular carcinoma (HCC) ranks the most common types of cancer worldwide. As the fourth leading cause of cancer-related deaths, its prognosis remains poor. Most patients developed HCC on the basis of chronic liver disease. Cirrhosis is an important precancerous lesion for HCC. However, the molecular mechanisms in HCC development are still unclear. To explore the changes at the level of transcriptome in this process, we performed RNA-sequencing on cirrhosis, HCC and paracancerous tissues. Continuously changing mRNA was identified using Mfuzz cluster analysis, then their functions were explored by enrichment analyses. Data of cirrhotic HCC patients were obtained from TCGA, and a fatty acid metabolism (FAM)-related prognostic signature was then established. The performance and immunity relevance of the signature were verified in internal and external datasets. Finally, we validated the expression and function of ADH1C by experiments. As a result, 2012 differently expressed mRNA were identified by RNA-sequencing and bioinformatics analyses. Fatty acid metabolism was identified as a critical pathway by enrichment analyses of the DEGs. A FAM-related prognostic model and nomogram based on it were efficient in predicting the prognosis of cirrhotic HCC patients, as patients with higher risk scores had shorter survival time. Risk scores calculated by the signature were then proved to be associated with a tumor immune environment. ADH1C were downregulated in HCC, while silence of ADH1C could significantly promote proliferation and motility of the HCC cell line.
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spelling doaj.art-880085f083eb4bb1a2904b41b6f2988e2023-11-30T21:23:21ZengMDPI AGBiomolecules2218-273X2023-01-0113114110.3390/biom13010141HCC: RNA-Sequencing in CirrhosisHaoyu Wang0Wenjie Shi1Jing Lu2Yuan Liu3Wei Zhou4Zekun Yu5Shengying Qin6Junwei Fan7Department of General Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaDepartment of General Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaDepartment of General Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaDepartment of General Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of General Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaHepatocellular carcinoma (HCC) ranks the most common types of cancer worldwide. As the fourth leading cause of cancer-related deaths, its prognosis remains poor. Most patients developed HCC on the basis of chronic liver disease. Cirrhosis is an important precancerous lesion for HCC. However, the molecular mechanisms in HCC development are still unclear. To explore the changes at the level of transcriptome in this process, we performed RNA-sequencing on cirrhosis, HCC and paracancerous tissues. Continuously changing mRNA was identified using Mfuzz cluster analysis, then their functions were explored by enrichment analyses. Data of cirrhotic HCC patients were obtained from TCGA, and a fatty acid metabolism (FAM)-related prognostic signature was then established. The performance and immunity relevance of the signature were verified in internal and external datasets. Finally, we validated the expression and function of ADH1C by experiments. As a result, 2012 differently expressed mRNA were identified by RNA-sequencing and bioinformatics analyses. Fatty acid metabolism was identified as a critical pathway by enrichment analyses of the DEGs. A FAM-related prognostic model and nomogram based on it were efficient in predicting the prognosis of cirrhotic HCC patients, as patients with higher risk scores had shorter survival time. Risk scores calculated by the signature were then proved to be associated with a tumor immune environment. ADH1C were downregulated in HCC, while silence of ADH1C could significantly promote proliferation and motility of the HCC cell line.https://www.mdpi.com/2218-273X/13/1/141hepatocellular carcinomacirrhosisRNA-sequencingprognostic signaturefatty acid metabolism
spellingShingle Haoyu Wang
Wenjie Shi
Jing Lu
Yuan Liu
Wei Zhou
Zekun Yu
Shengying Qin
Junwei Fan
HCC: RNA-Sequencing in Cirrhosis
Biomolecules
hepatocellular carcinoma
cirrhosis
RNA-sequencing
prognostic signature
fatty acid metabolism
title HCC: RNA-Sequencing in Cirrhosis
title_full HCC: RNA-Sequencing in Cirrhosis
title_fullStr HCC: RNA-Sequencing in Cirrhosis
title_full_unstemmed HCC: RNA-Sequencing in Cirrhosis
title_short HCC: RNA-Sequencing in Cirrhosis
title_sort hcc rna sequencing in cirrhosis
topic hepatocellular carcinoma
cirrhosis
RNA-sequencing
prognostic signature
fatty acid metabolism
url https://www.mdpi.com/2218-273X/13/1/141
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