Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma

HCC remains a lethal cancer type, with early detection being critical for improved patient outcomes. This study introduces a comprehensive methodological approach to identify the ITGA6 gene as a potential blood marker for early HCC (eHCC) detection. We initially analyzed the GSE114564 dataset encomp...

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Main Authors: Hyung Seok Kim, Jung Hwan Yoon, Geum Ok Baek, Moon Gyeong Yoon, Ji Eun Han, Hyo Jung Cho, Soon Sun Kim, Jee-Yeong Jeong, Jae Youn Cheong, Jung Woo Eun
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/16/4156
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author Hyung Seok Kim
Jung Hwan Yoon
Geum Ok Baek
Moon Gyeong Yoon
Ji Eun Han
Hyo Jung Cho
Soon Sun Kim
Jee-Yeong Jeong
Jae Youn Cheong
Jung Woo Eun
author_facet Hyung Seok Kim
Jung Hwan Yoon
Geum Ok Baek
Moon Gyeong Yoon
Ji Eun Han
Hyo Jung Cho
Soon Sun Kim
Jee-Yeong Jeong
Jae Youn Cheong
Jung Woo Eun
author_sort Hyung Seok Kim
collection DOAJ
description HCC remains a lethal cancer type, with early detection being critical for improved patient outcomes. This study introduces a comprehensive methodological approach to identify the ITGA6 gene as a potential blood marker for early HCC (eHCC) detection. We initially analyzed the GSE114564 dataset encompassing various stages of liver disease, identifying 972 differentially expressed genes in HCC. A refined analysis yielded 59 genes specifically differentially expressed in early HCC, including ITGA6. Subsequent validation in multiple datasets confirmed the consistent upregulation of ITGA6 in HCC. In addition, when analyzing progression-free survival (PFS) within the entire patient cohort and overall survival (OS) specifically among patients classified as tumor grade G1, the group of patients characterized by high expression levels of ITGA6 displayed an elevated risk ratio in relation to prognosis. Further analyses demonstrated the predominant expression of ITGA6 in TECs and its enrichment in angiogenesis-related pathways. Additionally, positive correlations were found between ITGA6 expression and pro-tumorigenic immune cells, but not with anti-tumorigenic immune cells. Our study elucidates the potential of ITGA6 as a blood-based marker for HCC early detection and diagnosis and its complex interplay with the tumor microenvironment. Further research may lead to novel strategies for HCC management and patient care.
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spelling doaj.art-4701b8ee20e54f20bb61bc2eb81ad5762023-11-19T00:34:06ZengMDPI AGCancers2072-66942023-08-011516415610.3390/cancers15164156Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular CarcinomaHyung Seok Kim0Jung Hwan Yoon1Geum Ok Baek2Moon Gyeong Yoon3Ji Eun Han4Hyo Jung Cho5Soon Sun Kim6Jee-Yeong Jeong7Jae Youn Cheong8Jung Woo Eun9Department of Biochemistry, College of Medicine, Kosin University, Seo-gu, Busan 49267, Republic of KoreaDepartment of Pathology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of KoreaDepartment of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of KoreaDepartment of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of KoreaDepartment of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of KoreaDepartment of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of KoreaDepartment of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of KoreaDepartment of Biochemistry, College of Medicine, Kosin University, Seo-gu, Busan 49267, Republic of KoreaDepartment of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of KoreaDepartment of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of KoreaHCC remains a lethal cancer type, with early detection being critical for improved patient outcomes. This study introduces a comprehensive methodological approach to identify the ITGA6 gene as a potential blood marker for early HCC (eHCC) detection. We initially analyzed the GSE114564 dataset encompassing various stages of liver disease, identifying 972 differentially expressed genes in HCC. A refined analysis yielded 59 genes specifically differentially expressed in early HCC, including ITGA6. Subsequent validation in multiple datasets confirmed the consistent upregulation of ITGA6 in HCC. In addition, when analyzing progression-free survival (PFS) within the entire patient cohort and overall survival (OS) specifically among patients classified as tumor grade G1, the group of patients characterized by high expression levels of ITGA6 displayed an elevated risk ratio in relation to prognosis. Further analyses demonstrated the predominant expression of ITGA6 in TECs and its enrichment in angiogenesis-related pathways. Additionally, positive correlations were found between ITGA6 expression and pro-tumorigenic immune cells, but not with anti-tumorigenic immune cells. Our study elucidates the potential of ITGA6 as a blood-based marker for HCC early detection and diagnosis and its complex interplay with the tumor microenvironment. Further research may lead to novel strategies for HCC management and patient care.https://www.mdpi.com/2072-6694/15/16/4156hepatocellular carcinomaintegrin alpha-6prognostic markerblood markertumor endothelial cellstumor microenvironment
spellingShingle Hyung Seok Kim
Jung Hwan Yoon
Geum Ok Baek
Moon Gyeong Yoon
Ji Eun Han
Hyo Jung Cho
Soon Sun Kim
Jee-Yeong Jeong
Jae Youn Cheong
Jung Woo Eun
Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma
Cancers
hepatocellular carcinoma
integrin alpha-6
prognostic marker
blood marker
tumor endothelial cells
tumor microenvironment
title Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma
title_full Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma
title_fullStr Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma
title_full_unstemmed Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma
title_short Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma
title_sort tumor endothelial cells associated integrin alpha 6 as a promising biomarker for early detection and prognosis of hepatocellular carcinoma
topic hepatocellular carcinoma
integrin alpha-6
prognostic marker
blood marker
tumor endothelial cells
tumor microenvironment
url https://www.mdpi.com/2072-6694/15/16/4156
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