GULP1 as a Novel Diagnostic and Predictive Biomarker in Hepatocellular Carcinoma

Kim, Hyung Seok; Yoon, Jung Hwan; Choi, Ji Yi; Yoon, Moon Gyeong; Baek, Geum Ok; Kang, Minji; Jang, Se Ha; Park, Won; Go, Yunjin; Ng, Jestlin Tianthing; Nam, Suk Woo; Jeong, Jee-Yeong; Han, Ji Eun; Cho, Hyo Jung; Lim, Su Bin; Kim, Soon Sun; Cheong, Jae Youn; Eun, Jung Woo

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Original Article

GULP1 as a Novel Diagnostic and Predictive Biomarker in Hepatocellular Carcinoma

Hyung Seok Kim¹, Jung Hwan Yoon², Ji Yi Choi^3,4, Moon Gyeong Yoon³, Geum Ok Baek³, Minji Kang^3,4, Se Ha Jang^3,4, Won Park⁵, Yunjin Go^4,6, Jestlin Tianthing Ng^4,6, Suk Woo Nam², Jee-Yeong Jeong¹, Ji Eun Han³, Hyo Jung Cho³, Su Bin Lim⁶, Soon Sun Kim³, Jae Youn Cheong³, Jung Woo Eun³

¹Department of Biochemistry, College of Medicine, Kosin University; Seo-gu, Busan 49267, South Korea
²Department of Pathology, College of Medicine, The Catholic University of Korea; Seocho-gu, Seoul 06591, South Korea
³Department of Gastroenterology, Ajou University School of Medicine; 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, South Korea
⁴Department of Biomedical Sciences, Ajou University Graduate School of Medicine; 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, South Korea
⁵Department of Bioscience and Biotechnology, Graduate School, Chungnam National University; 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea
⁶Department of Biochemistry and Molecular Biology, Ajou University School of Medicine; 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, South Korea

Correspondence :

Jung Woo Eun ,
Tel: 82-31-219-4681, Fax: 82-31-219-4680, Email: jetaimebin@gmail.com

Received: November 19, 2024 Revised: February 3, 2025 Accepted: February 4, 2025
*Hyung Seok Kim and Jung Hwan Yoon contributed equally to this work.

ABSTRACT

Backgrounds/Aims
Hepatocellular carcinoma (HCC) is characterized by high recurrence and mortality, necessitating the identification of reliable biomarkers. In this study, we aimed to identify the predictive gene signatures for HCC recurrence and evaluate the efficiency of GULP PTB domain-containing engulfment adaptor 1 (GULP1) as a predictive and diagnostic marker and therapeutic target for HCC.
Methods
We analyzed genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases via least absolute shrinkage and selection operator Cox regression and 10-fold cross-validation, leading to the development of a 15-gene risk score model, which was validated using three independent datasets. Serum GULP1 and α-fetoprotein levels were assessed to determine the diagnostic accuracy of the model. Using clinical cohorts and patient sera, GULP1 roles were examined, and functional assays in vitro and in vivo were used to evaluate its effects on cell growth, epithelial–mesenchymal transition (EMT), ADP-ribosylation factor 6 activation, and β-catenin signaling.
Results
Our newly developed risk-score model accurately predicted recurrent HCC in all datasets. Among the 15 genes in the risk score model, GULP1 was overexpressed in patients with HCC and independently predicted HCC recurrence. Its expression modulation influenced cell growth and EMT, with observed effects on ADP-ribosylation factor 6 activation and β-catenin signaling pathways.
Conclusions
GULP1 is a crucial biomarker for HCC, serving as a non-invasive diagnostic and predictive tool. It also plays key roles in HCC progression. Our findings highlight the potential use of GULP1 in treatment strategies targeting EMT and HCC recurrence to improve the personalized care and patient outcomes.

KeyWords: Liver cancer; GULP1; Recurrence; Metastasis; Diagnosis