MDK (Midkine)

RNA immunoprecipitation confirmed that IGF2BP2 bound to MDK mRNA, and this binding was significantly diminished upon mutation of the top three predicted N6‑methyladenosine modification sites in MDK. These findings suggested that the IGF2BP2/MDK axis contributed to abnormal colonic epithelial proliferation under T2DM conditions and may represent a potential therapeutic target to reduce carcinoma risk in patients with diabetes.

Targeting the MDK/LRP1 axis with Resmetirom offers a promising therapeutic strategy for MASH-associated HCC, addressing both metabolic dysfunction and tumor progression.

These findings suggest that higher baseline serum midkine levels in premenopausal women are associated with a reduced long-term risk of ER + breast cancer. This challenges prior assumptions about midkine's uniformly pro-tumorigenic role and suggests it may be a context-dependent biomarker in breast cancer development.

This study demonstrates that LBX2-AS1 promotes CRC angiogenesis and activates the glycolysis via the miR-491-5p/MDK axis. LBX2-AS may serve as a novel diagnostic biomarker and potential therapeutic target for CRC.

This review examines MDK's molecular and biological functions in gastrointestinal cancers, emphasizing its clinical utility in diagnosis, prognosis, and therapy. By exploring the intricate mechanisms of MDK, this study aims to advance the development of novel, personalized therapeutic strategies to improve patient outcomes.

Our findings provide a comprehensive cellular atlas of CSCC, highlighting the association of CAFs in HPV infection and tumor progression of CSCC. These results also offer potential diagnostic and prognostic biomarkers for CSCC patients.

In summary, our study revealed the dynamics of tumor cells in lymph node metastasis in GC and identified a subtype of GC cells with potential metastatic capability. Our data suggest that necroptosis and the MDK-NCL signaling pathway may be involved in facilitating lymph node metastasis, providing new insights into the mechanisms of GC progression and potential therapeutic targets.

FAM49B knockdown significantly inhibited MDK expression and disrupted ECM-receptor interactions. FAM49B promotes immunosuppressive TME formation by mediating TAM polarization via the MDK-NCL axis, suggesting the FAM49B-MDK-NCL pathway as a potential therapeutic target for CRC metastasis.

Notably, MDK treatment drives tumor cells into the cell cycle, thereby increasing the therapeutic effect of busulfan. Furthermore, MDK promotes osteogenic differentiation of mesenchymal stem cells (MSC), contributing to the remodeling of the bone marrow microenvironment. In addition, type I IFN upregulates TNFSF10, leading to tumor cell death through mutual killing.

Functionally, GBM-derived MDK induced macrophages to secrete multiple cytokines and chemokines, suggesting its role in reshaping the tumor microenvironment. Our findings reveal MDK's previously underappreciated role in GBM aggressiveness and immune modulation, underscoring its potential as a biomarker and actionable therapeutic target for most GBM patients.

In GSE31210, the MDK expression significantly increased the risk of recurrence (HR 2.617 &lsqb;1.791-3.824], p < 0.001) and death (HR 2.495 &lsqb;1.429-4.356], p = 0.001), whereas patients with higher MDK expression also had worse recurrence-free survival (p = 0.006) and overall survival (p < 0.001). MDK was considered a putative candidate for predicting early recurrence in patients with stage IA LUAD.

MDK and TIMP1 significantly influence the prognosis and progression of LUAD and immune cell infiltration, highlighting their potential as targets for immunotherapy.