ABSTRACT
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Despite progress in the last decades, there are still no reliable biomarkers for the diagnosis of and prognosis for GC. Aberrant sialylation is a widespread critical event in the development of GC. Neuraminidases (Neu) and sialyltransferases (STs) regulate the ablation and addition of sialic acid during glycoconjugates biosynthesis, and they are a considerable source of biomarkers in various cancers. This study retrospectively characterized Neu3 and ST3Gal3 expression by immunohistochemistry in 71 paraffin-embedded GC tissue specimens and analyzed the relationship between their expression and the clinicopathological parameters. Neu3 expression was markedly increased in GC tissues compared with non-tumoral tissues (p<0.0001). Intratumoral ST3Gal3 staining was significantly associated with intestinal subtype (p=0.0042) and was negatively associated with angiolymphatic invasion (p=0.0002) and higher histological grade G3 (p=0.0066). Multivariate analysis revealed that ST3Gal3 positivity is able to predict Lauren's classification. No associations were found between Neu3 staining and clinical parameters. The in silico analysis of mRNA expression in GC validation cohorts corroborates the significant ST3Gal3 association with higher histological grade observed in our study. These findings suggest that ST3Gal3 expression may be an indicator for aggressiveness of primary GC.
Subject(s)
Stomach Neoplasms , Humans , N-Acetylneuraminic Acid , RNA, Messenger , Retrospective Studies , Sialyltransferases/genetics , Sialyltransferases/metabolism , Stomach Neoplasms/pathologyABSTRACT
Pancreatic ductal adenocarcinoma is one of the most aggressive tumors with a microenvironment marked by hypoxia and starvation. Galectin-3 has been evaluated in solid tumors and seems to present both pro/anti-tumor effects. So, this study aims to characterize the expression of Galectin-3 from pancreatic tumor cells and analyze its influence for cell survive and motility in mimetic microenvironment. For this, cell cycle and cell death were accessed through flow cytometry. Characterization of inside and outside Galectin-3 was performed through Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), immunofluorescence, Western blot, and ELISA. Consequences of Galectin-3 extracellular inhibition were investigated using cell death and scratch assays. PANC-1 showed increased Galectin-3 mRNA expression when cultivated in hypoxia for 24 and 48 h. After 24 h in simultaneously hypoxic/deprived incubation, PANC-1 shows increased Galectin-3 protein and secreted levels. For Mia PaCa-2, cultivation in deprivation was determinant for the increasing in Galectin-3 mRNA expression. When cultivated in simultaneously hypoxic/deprived condition, Mia PaCa-2 also presented increasing for the Galectin-3 secreted levels. Treatment of PANC-1 cells with lactose increased the death rate when cells were incubated simultaneously hypoxic/deprived condition. Therefore, it is possible to conclude that the microenvironmental conditions modulate the Galectin-3 expression on the transcriptional and translational levels for pancreatic cancer cells.
Subject(s)
Blood Proteins/metabolism , Galectins/metabolism , Nutrients/metabolism , Pancreatic Neoplasms/metabolism , Blood Proteins/genetics , Blood Proteins/isolation & purification , Cell Cycle , Cell Death , Cell Hypoxia , Galectins/genetics , Galectins/isolation & purification , Humans , Pancreatic Neoplasms/pathology , Tumor Cells, Cultured , Tumor MicroenvironmentABSTRACT
Gastric cancer (GC) is the second most common cause of cancer-related deaths in the world. This study aims to investigate the differential tissue expression of ppGalNAc-T15 and to evaluate its possible association with clinical-pathological parameters and outcome of gastric adenocarcinoma patients. For these 70 patients were evaluated the expression by immunohistochemistry to ppGalNAc-T15. Our results showed that 33 (47.1%) patients were ppGalNAC-T15+ positive and 37 (52.9%) negative. Positive staining for ppGalNAc-T15 was significantly present in patients older than 60 years (P=0.0306) and submitted to total gastrectomy (P=0.0087). Also, some results remained at the limit of significance as surgical standing (P=0.0562) and histological grade (P=0.0549). Therefore, the ppGalNAc-T15 immunoreactivity can be useful to understand the prognosis of patients with gastric cancer.
