Pan-Cancer Analysis and Experimental Validation of SOX4 as a Potential Diagnosis, Prognosis, and Immunotherapy Biomarker

Author:

Deng Xinna1,Wang Yashu2ORCID,Guo Hao1,Wang Qian1,Rao Shuting13,Wu Haijiang2

Affiliation:

1. Departments of Oncology, Hebei General Hospital, Shijiazhuang 050057, China

2. Department of Pathology, Hebei Medical University, Shijiazhuang 050011, China

3. Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050011, China

Abstract

Introduction: SOX4 plays an important role in tumorigenesis and cancer progression. The role of SOX4 in pan-cancer and its underlying molecular mechanism in liver hepatocellular carcinoma (LIHC) are not fully understood. In this study, a comprehensive analysis and experimental validation were performed to explore the function of SOX4 across tumor types. Methods: Raw data in regard to SOX4 expression in malignant tumors were downloaded from the TCGA and GTEx databases. The expression levels, prognostic values, genetic mutation, and DNA promoter methylation of SOX4 across tumor types were explored via systematic bioinformatics analysis. The ceRNA regulatory network, immune characteristics, and prognostic models were analyzed in LIHC. Finally, we conducted in vitro experiments including Western blotting, cell proliferative assay, trypan blue staining, and fluorescence microscopy to further explore the function of SOX4 in LIHC. Results: SOX4 expression was significantly upregulated in 24 tumor types. SOX4 expression level was strongly associated with unfavorable prognoses, genetic mutations, and DNA methylation levels across different tumor types. Especially in LIHC, LINC00152/hsa-miR-139-3p/SOX4 was identified as a crucial ceRNA network. Moreover, this study also provides insight into the roles of SOX4 expression in immune cell infiltration, macrophage polarization, immune subtype, molecular subtype, and immunomodulators, as well as the tumor immune microenvironment (TIME)-related prognosis, in LIHC. The study established six favorable prognostic models to predict LIHC prognosis based on the SOX4-associated genes. Finally, lenvatinib treatment can increase the expression of SOX4 in hepatocellular carcinoma cells and lead to drug resistance. Silencing SOX4 can effectively eliminate the drug resistance caused by lenvatinib treatment and inhibit the proliferation of cancer cells.Conclusions: This study highlights that SOX4 may serve as a promising therapeutic target for tumor treatment.

Funder

Natural Science Foundation of Hebei province

2022 government-funded clinical talents project of Hebei Province

333 Talent Project of Hebei Province

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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