ALDOB (Aldolase, Fructose-Bisphosphate B)

These findings indicate that FOXA2 promotes CPT-11 resistance by upregulating ALDOB-mediated fatty acid β-oxidation. Targeting the FOXA2/ALDOB axis may overcome chemoresistance in CRC.

IHC showed that the ALDOB level in ccRCC samples was notably diminished relative to that in the adjacent normal tissues. As a prospective predictive indicator for individuals with ccRCC, reduced ALDOB level exhibited strong correlations with clinical characteristics, unfavorable outcomes, and immune infiltration in individuals with ccRCC.

Further cell experiments revealed that ALDOB overexpression enhanced the expression of WNT signaling pathway-related proteins (β-catenin and c-myc), which in turn promoted PDL1 expression in CRC cells, inhibiting the proliferation and killing effect of CD8+ T cells in co-culture systems. Our findings disclose how ALDOB influences CD8+ T cell recruitment and antitumor immune function, proposing it as a potential target for the treatment of CRC.

Furthermore, tumor growth of mice was suppressed by sh-SUV39H1 transfection, chaetocin treatment, or F5446 treatment. In conclusion, SUV39H1 promoted GC progression by modulating the H3K9me3/ALDOB axis.

Finally, drug sensitivity analysis revealed that ALDOB increased the sensitivity of gastric cancer cells to most antitumor drugs, especially talazoparib, XAV939, and FTI-277. And ALDOB significantly inhibited proliferation and migration, delayed glycolysis in GC cells. Consequently, our study suggests that ALDOB may be a potential target for the clinical treatment of gastric cancer.

In addition, we have also discovered the effect of ALDOB in previous studies on other cancer types. Finally, we concluded that ALDOB may have potential reference value for immunotherapy and can also be used as an independent predictor of prognosis in KIRC.

Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p < 0.01).

Our study has revealed a novel mechanism by which a metabolic enzyme in tumor cells epigenetically modulates TGF-β signaling, thereby enabling cancer cells to evade immune surveillance and affect their response to immunotherapy.

The ALDOB/PDK1/lactate/CEACAM6 axis plays an essential role in CRC cell behavior and bioenergetic homeostasis, providing new insights into the involvement of CEACAM6 in CRC and the Warburg effect. These findings may lead to the development of new treatment strategies for CRC patients.

Pharmacological inhibition of GLUT1 or G6PD enhances the chemotherapy response of glucomet-PDAC. Our findings uncover potential metabolic heterogeneity related to differences in chemotherapy sensitivity in PDAC and develop a promising pharmacological strategy for patients with chemotherapy-resistant glucomet-PDAC through the combination of chemotherapy and GLUT1/ALDOB/G6PD axis inhibitors.

The increase in growth and cells' ability to migrate stimulated by ALDOB inhibition was partially impaired in cells under the influence of AKT inhibitors. The overall data highlights a novel target, the ALDOB/AKT signaling axis for the treatment of GC.

Conclusion The overexpression of ALDOB is associated with poor prognosis in CRC patients. The ALDOB/lactate/CEA axis might play an important role in CRC cell proliferation and 5-fluorouracil resistance.