UDP-glucose 6-dehydrogenase expression as a predictor of survival in patients with pulmonary adenocarcinoma

Abstract

Background: UDP-glucose-6-dehydrogenase (UGDH) plays an important role in the production of hyaluronic acid, an extracellular matrix component that is responsible for the promotion of normal cellular growth and migration. Increased levels of UGDH have been linked to the progression of epithelial cancers, such as those of the breast, colon and prostate. Therefore we aimed to analyze if the expression level of UGDH does also influence patients survival of lung cancer patients. Methods: UGDH expression levels were analyzed by immunohistochemistry in 96 samples of pulmonary adenocarcinoma (AC), 84 cases of squamous cell lung carcinoma (SQCLC) and 33 samples of small cell lung cancer (SCLC) and correlated with clinicopathologic characteristics and patient outcome. Results: UGDH was expressed in 62.5% cases of AC, 70.2% cases of SQCLC, and 48.5% cases of SCLC. In AC, expression of UGDH was significantly associated with lymph node metastasis and worse overall survival of the affected patients. However, UGDH expression had no significant correlation to prognosis in SQCLC or SCLC patients. Conclusions: In our study, expression of UGDH was associated with worse prognosis of patients with pulmonary adenocarcinoma so that expression of UGDH might help to guide treatment decisions. Furthermore, UGDH might present a potential novel drug target in AC as it displays inhibitable catalytic activity.

Two-Dimensional Polyacrylamide Gel Electrophoresis Coupled with Nanoliquid Chromatography–Tandem Mass Spectrometry-Based Identification of Differentially Expressed Proteins and Tumorigenic Pathways in the MCF7 Breast Cancer Cell Line Transfected for Jumping Translocation Breakpoint Protein Overexpression

“…Expression in Malignancies and Putative Neoplastic Effects Pathways Neoplastic Behavior PCBP2 poly(rC)-binding protein 2 isoform b RNA-binding protein, contributes to transcriptional and translational regulation [81,82] oncogene, promoter of GC [81], HCC, GBM, BC tissues, and cell lines [83] AT overexpression increases cholesterol synthesis and facilitates the stemness of BCSCs via activating PI3K/Akt signaling [82] depletion decreases GC cells viability and proliferation [81]; inhibits cell proliferation, colony formation, migration, invasion, in vivo tumor growth, and metastasis in BC [83] MCCC2 methylcrotonyl-CoA carboxylase 2 mitochondrial member of the biotin-dependent carboxylase superfamily oncogene overexpressed in HCC [84], BC [85], PCa [86], CRC [87] AT downregulation of survival-dependent leucine metabolism [84] knockdown expression reduces cell proliferation, migration, and invasion and glycolysis markers, glucose consumption, lactate secretion, and acetyl-CoA level [84]; promotes apoptosis [86] UGDH isoform 2 UDP-glucose 6-dehydrogenase metabolic enzyme associated with mesenchymal-like gene expression [88] upregulated in epithelial cancers, such as BC [88]; highly metastatic ovarian cancer cell lines [89]; GBM [90]; lung cancer [91] AT EMT inhibition, inactivation of ERK/MAPK, metabolic reprogramming, ECM remodeling [88] knockdown decreases cell motility, invasion, GAGs synthesis, and cell migration [90]; tumor growth, HA production, colony formation [88] ATP via OXPHOS, ectopically expressed on the surface of various cancer cells [94] participant in carcinogenesis in several tumors, overexpressed in BC, especially in luminal and HER2+ subtypes [94]; plasma membrane of highly invasive cells, including MDA-MB-231 BC cells [95]; GC [96] AT OXPHOS; overexpression induces cancer progression via FAK/AKT/MMP2 pathway [96] overexpression increases intracellular ATP in cancer cells, promoting migration, invasion [95],…”

“…UDP-glucose 6-dehydrogenase (UGDH) is a metabolic enzyme associated with mesenchymal-like gene expression [88]. UGDH has been found to be upregulated in epithelial cancers, including BC [88], highly metastatic ovarian cancer cell lines [89], GBM [90], and lung cancer [91]. UGDH knockdown decreases cell motility, invasion, glycosaminoglycan biosynthesis, cell migration [90], tumor growth, hyaluronic acid production, and colony formation [88] and induces cell cycle arrest in the G 0 /G 1 phase [89].…”