Coriandrum sativum improves prognosis in clear cell renal cell carcinoma by targeting NEK6 to modulate the immune...

Coriandrum sativum L. (coriander) is a medicinal herb with diverse pharmacological properties, but its molecular mechanism in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to systematically investigate the underlying mechanisms of coriander in ccRCC by multi-omics analysis. Active compounds were screened using Traditional Chinese Medicine Systems Pharmacology (TCMSP) and predicted targets identified via SwissTargetPrediction (STP) and Similarity ensemble approach (SEA). Transcriptomic data from GSE53757 were analysed with WGCNA and intersected with coriander targets. Key genes were selected using LASSO, SVM, and random forest models. NEK6 was further analysed for clinical relevance, methylation, immune association, single-cell expression, molecular docking and molecular dynamics simulation. Fourteen coriander compounds were identified, yielding 22 potential ccRCC-related targets. NEK6 and PYGL were consistently selected by all machine learning algorithms. NEK6 was overexpressed in ccRCC and associated with better prognosis, promoter hypomethylation, and lower mutation rates. NEK6 expression correlated with immune infiltration, particularly macrophages, and was enriched in tumour and myeloid cells at the single-cell level. Molecular docking and molecular dynamics simulation revealed strong and stable binding of luteolin, quercetin, and chryseriol to NEK6. NEK6 may function as a prognostic and immune-regulatory biomarker in ccRCC. Coriander flavonoids could target NEK6 to modulate the immune microenvironment, providing new insight into plant-based therapeutic strategies for ccRCC.