Systematic Investigation of the Multifaceted Role of SOX11 in Cancer

SIMPLE SUMMARY: The transcription factor SOX11 is a member of the SRY box-containing family. Recently, SOX11 research has shifted from embryogenesis to cancer development. Nevertheless, the roles of SOX11 in different cancer types remain controversial. Here, we systematically explored the characteristics of SOX11 by multiple omics analyses. Aberrant SOX11 expression has been observed in many types of human malignant tumors. Moreover, SOX11 expression could serve as an indicator of survival outcomes, tumor progression and cellular immune infiltration. Our work highlights the diverse role of SOX11 in different types of tumors, which points out several directions for future prospective studies on SOX11 in cancer. ABSTRACT: SRY-box transcription factor 11 (SOX11), as a member of the SOX family, is a transcription factor involved in the regulation of specific biological processes and has recently been found to be a prognostic marker for certain cancers. However, the roles of SOX11 in cancer remain controversial. Our study aimed to explore the various aspects of SOX11 in pan-cancer. The expression of SOX11 was investigated by the Genotype Tissue-Expression (GTEX) dataset and the Cancer Genome Atlas (TCGA) database. The protein level of SOX11 in tumor tissues and tumor-adjacent tissues was verified by human pan-cancer tissue microarray. Additionally, we used TCGA pan-cancer data to analyze the correlations among SOX11 expression and survival outcomes, clinical features, stemness, microsatellite instability (MSI), tumor mutation burden (TMB), mismatch repair (MMR) related genes and the tumor immune microenvironment. Furthermore, the cBioPortal database was applied to investigate the gene alterations of SOX11. The main biological processes of SOX11 in cancers were analyzed by Gene Set Enrichment Analysis (GSEA). As a result, aberrant expression of SOX11 has been implicated in 27 kinds of cancer types. Aberrant SOX11 expression was closely associated with survival outcomes, stage, tumor recurrence, MSI, TMB and MMR-related genes. In addition, the most frequent alteration of the SOX11 genome was mutation. Our study also showed the correlations of SOX11 with the level of immune infiltration in various cancers. In summary, our findings underline the multifaceted role and prognostic value of SOX11 in pan-cancer.