Machine learning model reveals roles of interferon‑stimulated genes in sorafenib‑resistant liver cancer

Seo,Deok Hwa; Park,Ji Woo; Jung,Hee Won; Kang,Min Woo; Kang,Byung Yoon; Lee,Dong Yeup; Lee,Jae Jun; Yoon,Seung Kew; Jang,Jeong Won; Ahn,Jae Gyoon; Sung,Pil Soo

doi:10.3892/ol.2024.14571

Machine learning model reveals roles of interferon‑stimulated genes in sorafenib‑resistant liver cancer

Authors:
- Deok Hwa Seo
- Ji Woo Park
- Hee Won Jung
- Min Woo Kang
- Byung Yoon Kang
- Dong Yeup Lee
- Jae Jun Lee
- Seung Kew Yoon
- Jeong Won Jang
- Jae Gyoon Ahn
- Pil Soo Sung
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Affiliations: Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea, Department of Computer Science and Engineering, Incheon National University, Incheon 22012, Republic of Korea, Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea
Published online on: July 15, 2024 https://doi.org/10.3892/ol.2024.14571
Article Number: 438
Copyright: © Seo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

HCC (Hepatocellular carcinoma) is the most common malignant tumor; however, the molecular pathogenesis of these tumors is not well understood. Sorafenib, an approved treatment for HCC, inhibits angiogenesis and tumor cell proliferation. However, only ~30% of patients are sensitive to sorafenib and most show disease progression, indicating resistance to sorafenib. The present study used machine learning to investigate several mechanisms related to sorafenib resistance in liver cancer cells. This revealed that unphosphorylated interferon‑stimulated genes (U‑ISGs) were upregulated in sorafenib‑resistant liver cancer cells, and the unphosphorylated ISGF3 (U‑ISGF3; unphosphorylated STAT1, unphosphorylated STAT2 and IRF9) complex was increased in sorafenib‑resistant liver cancer cells. Further study revealed that the knockdown of the U‑ISGF3 complex downregulated U‑ISGs. In addition, inhibition of the U‑ISGF3 complex downregulated cell viability in sorafenib‑resistant liver cancer cells. These results suggest that U‑ISGF3 induced sorafenib resistance in liver cancer cells. Also, this mechanism may also be relevant to patients with sorafenib resistance.

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