Expression and prognostic value of SEC13 across multiple tumour types and its association with the regulation by Pulsatilla chinensis: a multi-omics and Mendelian Randomization Study.

Abstract

Background: Cancer remains one of the leading causes of death worldwide. The lack of effective early diagnostic markers and comprehensive treatment strategies continues to limit progress in clinical outcomes. Although targeted therapies have brought some improvement, the need for more reliable and efficient treatment options persists. SEC13, a protein involved in cellular energy metabolism and nucleocytoplasmic transport, has been suggested to play a role in tumour progression. This study aims to explore the potential role of SEC13 across various types of cancer, with a particular focus on its value as a diagnostic and prognostic marker, using Mendelian randomization analysis.

Methods: In this study, we conducted a comprehensive analysis of SEC13 expression using data from TCGA and GTEx, and explored associated pathways through gene set enrichment analysis. Single-cell transcriptomic data were integrated to investigate the cell-type-specific expression of SEC13 within the tumour microenvironment. In parallel, we examined the regulatory potential of the traditional Chinese compound PC using publicly available gene expression profiles. Causal inference between SEC13 and cancer susceptibility was assessed through Mendelian randomization and data from the BEST database.

Results: SEC13 was found to be significantly upregulated in several cancer types. Higher expression levels appeared to be associated with more advanced tumour stages and poorer survival outcomes. However, Mendelian randomization did not provide clear evidence for a direct causal link between SEC13 and any of the six cancers studied (P-IVW > 0.05). Interestingly, a negative association was observed between SEC13 expression and chemotherapy sensitivity, which may point to a possible role in drug resistance. Additionally, single-cell analysis revealed marked expression of SEC13 in fibroblasts, tumour-associated macrophages, and endothelial cells, suggesting a possible role in immune modulation and microenvironmental remodelling.

Conclusions: These findings highlight the prognostic relevance of SEC13 across multiple cancers and suggest that it may be regulated by PC, potentially contributing to anti-tumour activity. While Mendelian randomization did not reveal a definitive causal link, the collective evidence warrants further investigation and external validation, particularly regarding SEC13 as a therapeutic target and its possible pharmacological modulation.