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Predictive metabolic biomarkers for the recurrent luminal breast cancer (BC) with hormone receptor (HR)-positive and human epidermal growth factor receptor type 2 (HER2)-negative are lacking. High levels of O-GlcNAcylation (O-GlcNAc) and pyruvate kinase isoenzyme M2 (PKM2) are associated with malignancy in BC, however, the association with the recurrence risk remains unclear. We first conduct survival analysis by using the METABRIC dataset to assess the correlation of PKM2 expression with BC clinical outcomes. Next, patients with HR+/HER2- luminal BC were recruited for PKM2/O-GlcNAc testing. Logistic regression and receiver operating characteristic curve analysis were performed to evaluate the 10-year DFS predicted outcome. Survival analysis of the METABRIC dataset revealed that high expression of PKM2 was significantly associated with worse overall survival in luminal BC. The high expression of O-GlcNAc or PKM2 was a significant independent marker for poor 10-year DFS using immunohistochemical analysis. The PKM2 or O-GlcNAc status was a significant predictor of DFS, with the combination of PKM2–O-GlcNAc status and T stage greatly enhancing the predictive outcome potential. In summary, O-GlcNAc, PKM2, and T stage serve as good prognostic discriminators in HR+/HER2− luminal BC.

Smad4, a common-mediator of Smads, plays a central role in forming complexes with receptor-phosphorylated Smads, and then transduces transforming growth factor (TGF)-β signals into the nuclei. Although many cellular factors are involved in TGF-β induced epithelial-to-mesenchymal transition (EMT) and cell migration, very little is known with the mechanism of Smad4 regulation on pro-oncogenes response by TGF-β. Herein, we demonstrate the interaction of Sentrin-specific protease 2 (SENP2) with Smad4 through SENP2 residue 363~400. The same segment is also important for desumoylation of Smad4, and able to relieve sumoylation-mediated TGF-β repression. The SENP2363~400 segment is critical for TGF-β-induced cell migration, which is correlated with SENP2363~400 deletion mutant failed to increase matrix metalloproteinase (MMP)-9 and EMT marker gene expression. Moreover, our results suggest that the interaction and desumoylation between SENP2 and Smad4 promote cell migration in triple-negative breast cancer cells. Altogether, our data show how SENP2 regulates its substrate for desumoylation, and also the role of SENP2 in TGF-β induced cancer cell migration.

The use of blood plasma biomarkers in gastric cancer (GC) management is limited due to a lack of reliable biomarkers. An LC‐MS/MS assay and a bioinformatic analysis were performed to identify blood plasma biomarkers in a GC discovery cohort. The data obtained were verified and validated by western blotting and an ELISA in an independent study cohort. A label‐free quantification analysis of the MS data using PEAKS7 software found that four plasma proteins of apolipoprotein C‐1, gelsolin, sex hormone‐binding globulin (SHBG), and complement component C4‐A were significantly overexpressed in GC patients. A western blot assay of these plasma proteins showed that only SHBG was consistently overexpressed in the patient group. ELISA measurement of SHBG blood plasma levels confirmed that the patient group had significantly higher SHBG levels than the control group. SHBG levels in the patient group remained significantly higher after being stratified by gender, age, and disease stage. These findings show that LC‐MS/MS is powerful and highly sensitive for plasma biomarker discovery, and SHBG could be a potential plasma biomarker for GC management.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.