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Increase in sialylation and branching in the mouse serum N-glycome correlates with inflammation and ovarian tumour progression.

ABSTRACT: Ovarian cancer is the most lethal gynaecological cancer and is often diagnosed in late stage, often as the result of the unavailability of sufficiently sensitive biomarkers for early detection, tumour progression and tumour-associated inflammation. Glycosylation is the most common posttranslational modification of proteins; it is altered in cancer and therefore is a potential source of biomarkers. We investigated the quantitative and qualitative effects of anti-inflammatory (acetylsalicylic acid) and pro-inflammatory (thioglycolate and chlorite-oxidized oxyamylose) drugs on glycosylation in mouse cancer serum. A significant increase in sialylation and branching of glycans in mice treated with an inflammation-inducing compound was observed. Moreover, the increases in sialylation correlated with increased tumour sizes. Increases in sialylation and branching were consistent with increased expression of sialyltransferases and the branching enzyme MGAT5. Because the sialyltransferases are highly conserved among species, the described changes in the ovarian cancer mouse model are relevant to humans and serum N-glycome analysis for monitoring disease treatment and progression might be a useful biomarker.

SUBMITTER: Saldova R

PROVIDER: S-EPMC3758313 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Increase in sialylation and branching in the mouse serum N-glycome correlates with inflammation and ovarian tumour progression.

Saldova Radka R Piccard Helene H Pérez-Garay Marta M Harvey David J DJ Struwe Weston B WB Galligan Marie C MC Berghmans Nele N Madden Stephen F SF Peracaula Rosa R Opdenakker Ghislain G Rudd Pauline M PM

PloS one 20130830 8

Ovarian cancer is the most lethal gynaecological cancer and is often diagnosed in late stage, often as the result of the unavailability of sufficiently sensitive biomarkers for early detection, tumour progression and tumour-associated inflammation. Glycosylation is the most common posttranslational modification of proteins; it is altered in cancer and therefore is a potential source of biomarkers. We investigated the quantitative and qualitative effects of anti-inflammatory (acetylsalicylic acid ...[more]

PMID: 24023608

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Project description:BackgroundOvarian cancer is the most fatal gynecologic malignancy worldwide due to its vagueness, delay in diagnosis, recurrence, and drug resistance. Therefore, a new type of ovarian cancer treatment prediction biomarker is urgently needed to supplement existing tools. A total of 230 people participated in this study. Out of this figure, 100 participants were patients who underwent an ovarian tumor operation, another 100 participants were ovarian benign patients, and the remaining 30 participants were healthy women. Cancer (experimental) group were 100 patients who underwent ovarian tumor operation, while the control groups were 130 participants consisting of 100 ovarian benign patients and 30 healthy women. Levels of SAA, carbohydrate antigen-125 (CA-125), and human epididymis protein 4 (HE4) were assessed using standard laboratory protocols. A total of 5 ovarian cancer tissues and paracancerous tissues were collected and then stored at -?80?°C until the qRT-PCR assay was conducted.ResultsThe ROC curve of SAA concentration in ovarian cancer was plotted to obtain the area under the curve AUC?=?0.889, the cut-off value 17.05?mg/L, the sensitivity 78.4% and specificity 86.5%. Compared with pretreatment, the level of serum SAA decreased significantly after treatment. The results revealed that there was a significant correlation between the level of serum SAA and advanced FIGO stage, histology subtype, lymphatic invasion, and distant metastasis (p =?0.003,0.002,0.000 and 0.001). The quantitative Reverse transcription polymerase chain reaction (qRT-PCR) assay revealed that the Messenger RNA (mRNA) of SAA-1 and SAA-4 was much higher in cancer tissues than in adjacent tissues, and MMPs was up-regulation including MMP-1, MMP-9 and MMP- 12 in OVCAR-3 cell stimulated by SAA. The transwell assay revealed that SAA could promote OVCAR-3 cell migration. Moreover, SAA can regulate EMT markers and promote AKT pathway activation.ConclusionsIn summary, our results demonstrated that SAA may be a potential diagnosis and treatment prediction biomarker. The SAA promotes OVCAR-3 cell migration by regulating MMPs and EMT which may correlate with AKT pathway activation.

Project description:BackgroundGliomas are tumours arising mostly from astrocytic or oligodendrocytic precursor cells. These tumours are classified according to the updated WHO classification from 2021 in 4 grades depending on molecular and histopathological criteria. Despite novel multimodal therapeutic approaches, the vast majority of gliomas (WHO grade III and IV) are not curable. The circadian clock is an important regulator of numerous cellular processes and its dysregulation had been found during the progression of many cancers, including gliomas.ResultsIn this study, we explore expression patterns of clock-controlled genes in low-grade glioma (LGG) and glioblastoma multiforme (GBM) and show that a set of 45 clock-controlled genes can be used to distinguish GBM from normal tissue. Subsequent analysis identified 17 clock-controlled genes with a significant association with survival. The results point to a loss of correlation strength within elements of the circadian clock network in GBM compared to LGG. We further explored the progression patterns of mutations in LGG and GBM, and showed that tumour suppressor APC is lost late both in LGG and GBM. Moreover, HIF1A, involved in cellular response to hypoxia, exhibits subclonal losses in LGG, and TERT, involved in the formation of telomerase, is lost late in the GBM progression. By examining multi-sample LGG data, we find that the clock-controlled driver genes APC, HIF1A, TERT and TP53 experience frequent subclonal gains and losses.ConclusionsOur results show a higher level of disrgulation at the gene expression level in GBM compared to LGG, and indicate an association between the differentially expressed clock-regulated genes and patient survival in both LGG and GBM. By reconstructing the patterns of progression in LGG and GBM, our data reveals the relatively late gains and losses of clock-regulated glioma drivers. Our analysis emphasizes the role of clock-regulated genes in glioma development and progression. Yet, further research is needed to asses their value in the development of new treatments.

Dataset Information

Increase in sialylation and branching in the mouse serum N-glycome correlates with inflammation and ovarian tumour progression.

Publications

Increase in sialylation and branching in the mouse serum N-glycome correlates with inflammation and ovarian tumour progression.

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