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J Cancer 2024; 15(9):2845-2865. doi:10.7150/jca.92768 This issue Cite

Research Paper

Comprehensive analysis of IGF2BP3 with expression features, prognosis, immune modulation and stemness in hepatocellular carcinoma and pan-cancer

Sha Qin^1#, Haoer Jin^1#, Yan Li¹, Xue Chen², Jiang He³, Juxiong Xiao⁴, Yan Qin⁴, Chuyi Liu⁵, Yitao Mao^4,6, Luqing Zhao^1,6✉

1. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China; and Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
2. Early Clinical Trial Center, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
3. Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
4. Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
5. College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, China.
6. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
#These authors contributed equally to this work.

✉ Corresponding author: Dr. Luqing Zhao, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China, E-mail: luqingzhaoedu.cn.

Abstract

Insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a critical m6A reader. It encodes proteins that contain several KH domains, which are important in RNA binding, RNA synthesis and metabolism. Lots of researches have studied the malignant potential of m6A readers in tumors. However, the biological functional analysis of IGF2BP3 in hepatocellular carcinoma (HCC) and pan-cancer is not comprehensive. In this study, we used a bioinformatics approach to comprehensively analyze the significance of IGF2BP3 in HCC through analyzing its expression, mutation, prognosis, protein-protein interaction (PPI) network, functional enrichment, and the correlation with ferroptosis, stemness as well as immune modulation in HCC. IGF2BP3 presented a negative correlation with the ferroptosis molecule NFE2L2, and a positive correlation with the ferroptosis molecule SLC1A5 as well as the immune checkpoint HAVCR2. In addition, we also analyzed IGF2BP3 expression, prognosis and immune modulation in pan-cancer, revealing the prognostic value of IGF2BP3 in a variety of tumors. Finally, we verified the biological functions of IGF2BP3 in HCC through various experiments. The data showed that IGF2BP3 may enhance the proliferation, colony formation and invasion capacities of HCC cells, and IGF2BP3 is mainly positively correlated with the expression level of stemness marker SOX2. In conclusion, IGF2BP3 had a potential to be a new perspective biomarker in forecasting the immune response, ferroptosis, stemness and prognosis of HCC or even pan-cancer.

Keywords: IGF2BP3, expression features, prognosis, immune modulation, hepatocellular carcinoma (HCC), pan-cancer analysis.

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