Targeting LRRC41 as a potential therapeutic approach for hepatocellular carcinoma

Jun Li; Chenjie Qin; Yicheng Wu; Sheng Cheng; Yuanqing Wang; Huijie Chen; Fangli Chen; Bingdi Chen; Jutang Li

doi:10.3389/fmolb.2023.1300294

Targeting LRRC41 as a potential therapeutic approach for hepatocellular carcinoma

Front Mol Biosci. 2023 Dec 21:10:1300294. doi: 10.3389/fmolb.2023.1300294. eCollection 2023.

Authors

Jun Li^#¹, Chenjie Qin^#², Yicheng Wu^#³, Sheng Cheng⁴, Yuanqing Wang⁵, Huijie Chen⁶, Fangli Chen⁷, Bingdi Chen¹, Jutang Li⁴

Affiliations

¹ The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai, China.
² State Key Laboratory of Systems Medicine for Cancer, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Vascular and Endovascular Surgery, Changzheng Hospital Affiliated to the Naval Medical University, Shanghai, China.
⁴ Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
⁶ Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Department of Hematology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, characterized by high mortality rate. In clinical practice, several makers of liver cancer, such as VEGFR1, FGFR1 and PDGFRα, were identified and their potentials as a therapeutic target were explored. However, the unsatisfied treatment results emphasized the needs of new therapeutic targets. Methods: 112 HCC patients samples were obtained to evaluate the expression of LRRC41, SOX9, CD44, and EPCAM in HCC, combined with prognosis analysis. A DEN-induced HCC rat model was constructed to verify the expression of LRRC41 and SOX9 in HCC and lung metastasis tissues. Immune score evaluation was analysized by bioinformatics methods. Network pharmacology was performed to explored the potential FDA-approved drugs targeting LRRC41. Results: Through analysis of the Timer database and tissue micro-array, we confirmed that LRRC41 was over-expressed in HCC and exhibited a significant positive correlation with recurrence and metastasis. Immunohistochemistry staining of human HCC tissue samples revealed significant upregulation of LRRC41, SOX9, CD44, and EPCAM, with LRRC41 showing a positive correlation with SOX9, CD44, and EPCAM expression. UALCAN database analysis indicated that LRRC41 and SOX9 contribute to poor prognosis whereas CD44 and EPCAM did not demonstrate the same significance. Furthermore, analysis of a DEN-induced HCC rat model confirmed the significantly elevated expression of LRRC41 and SOX9 in HCC and lung metastasis tissues. Drug sensitivity analysis and molecular docking targeting LRRC41 identified several FDA-approved drugs, which may have potential antitumor effects on HCC by targeting LRRC41. Conclusion: Our findings highlight the role of LRRC41 overexpression in promoting HCC progression and its association with a poor prognosis. Drug sensitivity analysis and molecular docking shows several FDA-approved drugs may be potential therapeutic targets for HCC. Targeting LRRC41 may hold promise as a potential therapeutic strategy for HCC.

Keywords: LRRC41; biomarker; drug therapy; hepatocellular carcinoma; prognosis.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The Open Project of Key Laboratory of Shanghai Municipal Health Commission funded this study No. ZDSYS-2021-06. Funding information National Natural Science Foundation of China, Grant/Award Number: 82103058; Shanghai Municipal Health and Family Planning Commission Foundation, Grant/Award Number: 20214Y036.