Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic response

PurposeCancer remains a major global cause of death, with rising incidence influenced by environmental factors. The THOC5 gene, part of the THO complex, has emerged as a potential regulator in cancer biology. This study investigates THOC5 expression across various cancers, its role in prognosis, and...

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Main Authors: Jin-Shu Pang, Yu Yang, Li Liang, Yu-Jia Zhao, Jin-Dan Li, Li-Peng Li, Xue-Xin Wei, Rui-Zhi Gao, Rong Wen, Yun He, Hong Yang, Xiu-Mei Bai
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Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1596120/full
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author Jin-Shu Pang
Jin-Shu Pang
Yu Yang
Yu Yang
Li Liang
Yu-Jia Zhao
Jin-Dan Li
Li-Peng Li
Xue-Xin Wei
Rui-Zhi Gao
Rong Wen
Yun He
Hong Yang
Hong Yang
Hong Yang
Xiu-Mei Bai
Xiu-Mei Bai
author_facet Jin-Shu Pang
Jin-Shu Pang
Yu Yang
Yu Yang
Li Liang
Yu-Jia Zhao
Jin-Dan Li
Li-Peng Li
Xue-Xin Wei
Rui-Zhi Gao
Rong Wen
Yun He
Hong Yang
Hong Yang
Hong Yang
Xiu-Mei Bai
Xiu-Mei Bai
author_sort Jin-Shu Pang
collection DOAJ
description PurposeCancer remains a major global cause of death, with rising incidence influenced by environmental factors. The THOC5 gene, part of the THO complex, has emerged as a potential regulator in cancer biology. This study investigates THOC5 expression across various cancers, its role in prognosis, and its potential therapeutic implications, particularly in liver hepatocellular carcinoma (LIHC).MethodsWe analyzed THOC5 expression and its prognostic significance across various cancer types using globally available public datasets. Single-cell RNA sequencing, in-house RNA-seq, immunohistochemistry, and proteomic analysis were employed to further validate THOC5 expression and prognosis in LIHC. Functional assays, including wound-healing and Transwell migration, were performed following THOC5 knockdown in LIHC cell lines. A drug sensitivity analysis was performed to identify therapeutic agents associated with THOC5 expression levels.ResultsResults indicate that THOC5 is overexpressed in various cancers and correlates with unfavorable prognosis. In LIHC, both THOC5 mRNA and protein was confirmed to be overexpressed in LIHC elevated THOC5 correlated with advanced tumor stages and poor survival outcomes. THOC5 knockdown suppressed in vitro cell proliferation, migration, and invasion. Additionally, high THOC5 expression was linked to increased immune cell infiltration and enhanced sensitivity to certain chemotherapy agents, though it predicted poor response to immune checkpoint blockade therapy. Furthermore, high THOC5 was also indicated to activate several tumor signaling pathways, such as EGFR, Hypoxia and MAPK pathways.ConclusionTHOC5 could be a prognostic biomarker and therapeutic target in LIHC and various cancers, providing alternative treatment options when immunotherapy fails.
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spelling doaj-art-5a10e2c4bf124690a094f8d7640df0952025-08-20T03:44:07ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-08-011210.3389/fmed.2025.15961201596120Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic responseJin-Shu Pang0Jin-Shu Pang1Yu Yang2Yu Yang3Li Liang4Yu-Jia Zhao5Jin-Dan Li6Li-Peng Li7Xue-Xin Wei8Rui-Zhi Gao9Rong Wen10Yun He11Hong Yang12Hong Yang13Hong Yang14Xiu-Mei Bai15Xiu-Mei Bai16Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaGuangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaGuangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaGuangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, ChinaCollaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, ChinaGuangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, ChinaPurposeCancer remains a major global cause of death, with rising incidence influenced by environmental factors. The THOC5 gene, part of the THO complex, has emerged as a potential regulator in cancer biology. This study investigates THOC5 expression across various cancers, its role in prognosis, and its potential therapeutic implications, particularly in liver hepatocellular carcinoma (LIHC).MethodsWe analyzed THOC5 expression and its prognostic significance across various cancer types using globally available public datasets. Single-cell RNA sequencing, in-house RNA-seq, immunohistochemistry, and proteomic analysis were employed to further validate THOC5 expression and prognosis in LIHC. Functional assays, including wound-healing and Transwell migration, were performed following THOC5 knockdown in LIHC cell lines. A drug sensitivity analysis was performed to identify therapeutic agents associated with THOC5 expression levels.ResultsResults indicate that THOC5 is overexpressed in various cancers and correlates with unfavorable prognosis. In LIHC, both THOC5 mRNA and protein was confirmed to be overexpressed in LIHC elevated THOC5 correlated with advanced tumor stages and poor survival outcomes. THOC5 knockdown suppressed in vitro cell proliferation, migration, and invasion. Additionally, high THOC5 expression was linked to increased immune cell infiltration and enhanced sensitivity to certain chemotherapy agents, though it predicted poor response to immune checkpoint blockade therapy. Furthermore, high THOC5 was also indicated to activate several tumor signaling pathways, such as EGFR, Hypoxia and MAPK pathways.ConclusionTHOC5 could be a prognostic biomarker and therapeutic target in LIHC and various cancers, providing alternative treatment options when immunotherapy fails.https://www.frontiersin.org/articles/10.3389/fmed.2025.1596120/fullTHOC5hepatocellular carcinomaexpressionprognosisICB therapy
spellingShingle Jin-Shu Pang
Jin-Shu Pang
Yu Yang
Yu Yang
Li Liang
Yu-Jia Zhao
Jin-Dan Li
Li-Peng Li
Xue-Xin Wei
Rui-Zhi Gao
Rong Wen
Yun He
Hong Yang
Hong Yang
Hong Yang
Xiu-Mei Bai
Xiu-Mei Bai
Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic response
Frontiers in Medicine
THOC5
hepatocellular carcinoma
expression
prognosis
ICB therapy
title Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic response
title_full Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic response
title_fullStr Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic response
title_full_unstemmed Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic response
title_short Elevated THOC5 expression in liver cancer and its implications for tumor progression and therapeutic response
title_sort elevated thoc5 expression in liver cancer and its implications for tumor progression and therapeutic response
topic THOC5
hepatocellular carcinoma
expression
prognosis
ICB therapy
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1596120/full
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