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ABSTRACT Colorectal cancer is a prevalent malignancy, with colon adenocarcinoma (COAD) representing its most common histological subtype. Although most stage I patients remain disease‐free after treatment, a subset rapidly progresses to advanced disease with markedly reduced survival. Therefore, identifying early molecular warning signals in stage I patients is essential for timely intervention. In this study, integrated datasets from The Cancer Genome Atlas and Genotype‐Tissue Expression projects were analysed using the landscape dynamic network biomarker ( l ‐DNB) approach to identify progression biomarkers (PBs) for COAD. Twenty PBs were identified, among which succinate dehydrogenase complex flavoprotein subunit A (SDHA) was selected for further investigation. The L1000CDS 2 database was subsequently queried utilizing these identified PBs, identifying Cucurbitacin I (CuI) as a promising therapeutic component against COAD. Molecular docking and molecular dynamics simulations demonstrated stable binding between CuI and SDHA, with a binding energy of −9.44 kcal/mol and an RMSD of 2.0 ± 0.3 Å. Subsequent in vitro experiments demonstrated that CuI treatment upregulated SDHA expression and inhibited activation of the NF‐κB pathway. Collectively, these findings suggest that the identified PBs may serve as early‐warning indicators for stage I COAD patients and that CuI suppresses COAD cell proliferation, potentially through the SDHA/NF‐κB axis, highlighting its promise as a potential therapeutic candidate.
Zhao et al. (Mon,) studied this question.