High Transaldolase 1 expression predicts poor survival of patients with upper tract urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) is a rare tumor with an incidence that varies greatly between Eastern and Western countries. Transaldolase 1 (TALDO1) is a rate-limiting enzyme of the pentose phosphate pathway. In humans, aberrant TALDO1 activity has been implicated in various autoimmune diseases and malignancies; however, the function of TALDO1 in UTUC has not been previously investigated. Here we evaluated the clinical significance of TALDO1 expression in 115 paraffin-embedded tumor samples from patients with UTUC using immunohistochemistry. Our results demonstrated that there was an association between high TALDO1 expression and advanced stage (P = 0.011), tumor size (P = 0.005), tumor location (P = 0.047), distant metastases (P = 0.023), local recurrence (P = 0.002), and cancer death (P = 0.003). Using univariate and multivariate analyses, we found that chemotherapy was an independent factor for bladder recurrence-free survival. Late stage (III/IV) and high TALDO1 expression were independent prognostic factors for progression-free and cancer-specific survival. In summary, increased TALDO1 expression in UTUC was significantly correlated with late stage, tumor size, tumor location, distant metastases, local recurrence, and cancer death. Therefore, high TALDO1 expression could be a predictor of poor survival in patients with UTUC. Further studies are necessary to investigate the role of TALDO1 in UTUC development.

Prognostic and Immune Infiltration Analysis of Transaldolase 1 (TALDO1) in Hepatocellular Carcinoma.

Background: Transaldolase 1 (TALDO1) deficiency was associated with hepatocellular carcinoma (HCC), but the association between TALDO1 and prognosis in HCC remains unclear. Material and Methods: RNA-seq and clinical data of HCC from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed. CCK8 and EdU assays were utilized to examine the effect of TALDO1 on HCC proliferation. Transwell assay was used to explore the effect of TALDO1 on HCC migration. Western Blot was applied to detected the expression levels of pathway-related proteins. Results: TALDO1 mRNA level was higher in HCC tissues than in control normal tissues in TCGA and GEO databases (P<0.001, P<0.001). Expression of TALDO1 mRNA was associated with histologic grade (P=0.021). Multivariate regression analysis revealed that high TALDO1 mRNA expression was an independent risk factor for prognosis (P<0.001). High expression of TALDO1 had poor overall survival (OS) (P=0.046). Additionally, Nomogram prognostic model of TALDO1 and clinicopathological parameters could predict the prognostic OS of HCC patients. Functional enrichment and immune infiltration analysis revealed that TALDO1 negatively regulates immune response. Furthermore, knockdown TALDO1 expression suppressed the proliferation and migration ability of HCC cells. Mechanistically, TALDO1 leaded to activation of the mitogen-activated protein kinase (MAPK) pathway and enhancement of epithelial-mesenchymal transition (EMT). Conclusion: Our findings demonstrated that TALDO1 could serve as a promising novel biomarker for HCC patients, which might modulate the immune microenvironment resulting in a poor prognosis.

Insulin priming effect on estradiol-induced breast cancer metabolism and growth.

Diabetes is a risk factor for breast cancer development and is associated with poor prognosis for breast cancer patients. However, the molecular and biochemical mechanisms underlying the association between diabetes and breast cancer have not been fully elucidated. Here, we investigated estradiol response in MCF-7 breast cancer cells with or without chronic exposure to insulin. We found that insulin priming is necessary and specific for estradiol-induced cancer cell growth, and induces anaplerotic shunting of glucose into macromolecule biosynthesis in the estradiol treated cells. Treatment with ERK or Akt specific inhibitors, U0126 or LY294002, respectively, suppressed estradiol-induced growth. Interestingly, molecular analysis revealed that estradiol treatment markedly increases expression of cyclin A and B, and decreases p21 and p27 in the insulin-primed cells. In addition, estradiol treatment activated metabolic genes in pentose phosphate (PPP) and serine biosynthesis pathways in the insulin-primed cells while insulin priming decreased metabolic gene expression associated with glucose catabolism in the breast cancer cells. Finally, we found that anti-diabetic drug metformin and AMPK ligand AICAR, but not thiazolidinediones (TZDs), specifically suppress the estradiol-induced cellular growth in the insulin-primed cells. These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.