Exploring the role of CD13 and inflammatory factors in radiation enteritis: insights from high-throughput proteomics and Mendelian randomization analysis.

BACKGROUND

Radiation enteritis (RE) is an unavoidable complication during radiotherapy for pelvic malignancies, characterized by chronic inflammation, fibrosis, and vascular injury in the intestinal tissue. Currently, there is a lack of research that delves into the relationship between inflammatory factors and key proteins in RE.

METHODS

This study employed high-throughput proteomics to analyze intestinal tissues from RE rats and healthy controls, identifying differentially expressed key proteins. The degree of intestinal damage was validated through HE staining. Furthermore, five Mendelian randomization methods were used to analyze the causal relationship between 70 serum circulating inflammatory factors and CD13 levels. Sensitivity analyses, including heterogeneity tests, leave-one-out tests, and horizontal pleiotropy tests, were performed to ensure the robustness and reliability of the results.

RESULTS

CD13 was identified as a key differentially expressed protein, with its expression significantly upregulated in RE rats and positively correlated with disease severity. Bidirectional Mendelian randomization analysis revealed causal relationships between CD13 and four inflammatory factors: increased levels of CCL28 and EN-RAGE may promote the rise in CD13, while increased levels of TAM-binding protein may be associated with decreased CD13 levels. Additionally, higher CD13 levels were found to be associated with increased levels of interleukin-12. Sensitivity analyses indicated good consistency and reliability in terms of heterogeneity and pleiotropy for these exposure variables.

CONCLUSION

This study reveals the potential mechanistic role of CD13 in RE. Moreover, the identified CD13-associated inflammatory factors offer potential targets for the development of new prevention and treatment strategies, with significant clinical implications.