p38-MAPK/MSK1-mediated overexpression of histone H3 serine 10 phosphorylation defines distance-dependent prognostic value of negative resection margin in gastric cancer

摘要: Alterations in histone modifications are now well known to result epigenetic heterogeneity tumor tissues; however, their prognostic value and association with resection margins still remain poorly understood controversial. Further, histopathologically negative several cancers have been associated better prognosis of the disease. However, gastric cancer, despite a high rate R0 resection, considerably incidence loco-regional recurrence is observed. We believe alterations global post-translational could help identifying molecular signatures for defining true surgical also cancer patients. The present study compares level H3S10ph among paired confirmed disease-free (R0) proximal distal margin (PRM DRM) tissue samples GC patients (n = 101). Immunoblotting immune-histochemical analysis showed significantly (p < 0.01) higher compared margins. Along tumor, levels both PRM DRM correlated clinical parameters poor survival. Interestingly, case DRM, survival was only found patient group distance <4 cm. Further investigations revealed that increase tissues not due change cell cycle profile but rather an interphase-associated phenomenon. Moreover, ph-MSK1 ph-p38 decrease on p38 inhibition cells p38-MAPK/MSK1 pathway-mediated regulation cancer. Our provides first evidence p38-MAPK/MSK1-regulated predictive more aggressive phenotype margin. Importantly, our data gave new rationale exploration use MSK1 inhibitor therapy combination modifications, H4K16ac H4K20me3 along as markers.