Blood group antigens SLeX, SLeA, and LeY as prognostic markers in endometrial cancer

Kolben, Thomas; Müller, Lena; Meister, Sarah; Keilmann, Lucia; Buschmann, Christina; Trillsch, Fabian; Burges, Alexander; Czogalla, Bastian; Mitter, Sophie; Schmoeckel, Elisa; Corradini, Stefanie; Mahner, Sven; Jeschke, Udo; Kessler, Mirjana; Beyer, Susanne

doi:10.1007/s00432-022-04098-8

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…Regarding this result, we can speculate about an enzymatic complex comprising both enzymes, essential for protein Lewis X sialylation in LS174T cells. SLeX expression in cancer has been associated with patient's invasive tumors and dismal prognosis [12,41], and for this reason, one of our objectives was to evaluate the biological impact of inhibiting SLeX biosynthesis in selected GI cancer cells. We observed that SLeX inhibition did not affect cancer cell proliferation overall.…”

Section: Discussionmentioning

confidence: 99%

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility

Costa

Senra

Teixeira

et al. 2022

Preprint

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Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of β-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells. By immunofluorescent screening, we selected SLeX-positive GI cancer cell lines and silenced ST3GalIV expression via CRISPR/Cas9. Immunofluorescence and western blot analysis showed that ST3GalIV KO efficiently impaired SLeX expression in most cancer cell lines, with the exception of the colon cancer cell line LS174T. The impact of ST3GalIV KO in the biosynthesis of SLeX isomer SLeA and non sialylated Lewis X and A were also evaluated and overall, ST3GalIV KO led to a decreased expression of SLeA and an increased expression in both LeX and LeA. In addition, the abrogation of SLeX on GI cancer cells led to a reduction in cell motility. Furthermore, ST3GalVI KO was performed in LS174T ST3GalIV KO cells, resulting in the complete abolishment of SLeX expression and consequent reduced motility capacity of those cells. Overall, these findings portray ST3GalIV as the main, but not the only, enzyme driving the biosynthesis of SLeX in GI cancer cells, with a functional impact on cancer cell motility.

show abstract

Section: Discussionmentioning

confidence: 99%

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility

Costa

Senra

Teixeira

et al. 2022

Preprint

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show abstract

“…However, there are still some weakness. First, as this study focuses on routine laboratory biomarkers, some prognostic markers were not included, such as tumour sizes and blood group antigens [ 31 , 32 ]. In addition, histopathological evaluation has a strong association with EC prognosis and is generally taken as a cornerstone for EC classification.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a prognostic nomogram model incorporating routine laboratory biomarkers for preoperative patients with endometrial cancer

Cong,

Li,

et al. 2023

BMC Cancer

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Background Some biomarkers collected from routine laboratory tests have shown important value in cancer prognosis. The study aimed to evaluate the prognostic significance of routine laboratory biomarkers in patients with endometrial cancer (EC) and to develop credible prognostic nomogram models for clinical application. Methods A total of 727 patients were randomly divided into a training set and a validation set. Cox proportional hazards models were used to evaluate each biomarker’s prognostic value, and independent prognostic factors were used to generate overall survival (OS) and progression-free survival (PFS) nomgrams. The efficacy of the nomograms were evaluated by Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration curves, X-tile analysis and Kaplan‒Meier curves. Results Ten significant biomarkers in multivariate Cox analysis were integrated to develop OS and PFS nomograms. The C-indices of the OS- nomogram in the training and validation sets were 0.885 (95% confidence interval (CI), 0.810–0.960) and 0.850 (95% CI, 0.761–0.939), respectively; those of the PFS- nomogram in the training and validation sets were 0.903 (95% CI, 0.866–0.940) and 0.825 (95% CI, 0.711–0.939), respectively. ROC, DCA and calibration curves showed better clinical application value for the nomograms incorporating routine laboratory biomarkers. X-tile analysis and Kaplan‒Meier curves showed that the nomograms were stable and credible in evaluating patients at different risks. Conclusions Nomogram models incorporating routine laboratory biomarkers, including NLR, MLR, fibrinogen, albumin and AB blood type, were demonstrated to be simple, reliable and favourable in predicting the outcomes of patients with EC.

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“…SLeX expression in cancer has been associated with patient’s invasive tumors and dismal prognosis [ 12 , 43 ], and for this reason, one of our objectives was to evaluate the biological impact of inhibiting SLeX biosynthesis in selected GI cancer cells. We observed that SLeX inhibition did not affect cancer cell proliferation overall.…”

Section: Discussionmentioning

confidence: 99%

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility

et al. 2023

View full text Add to dashboard Cite

Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of β-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells. By immunofluorescent screening, we selected SLeX-positive GI cancer cell lines and silenced ST3GalIV expression via CRISPR/Cas9. Flow cytometry, immunofluorescence and western blot analysis showed that ST3GalIV KO efficiently impaired SLeX expression in most cancer cell lines, with the exception of the colon cancer cell line LS174T. The impact of ST3GalIV KO in the biosynthesis of SLeX isomer SLeA and non sialylated Lewis X and A were also evaluated and overall, ST3GalIV KO led to a decreased expression of SLeA and an increased expression in both LeX and LeA. In addition, the abrogation of SLeX on GI cancer cells led to a reduction in cell motility. Furthermore, ST3GalVI KO was performed in LS174T ST3GalIV KO cells, resulting in the complete abolishment of SLeX expression and consequent reduced motility capacity of those cells. Overall, these findings portray ST3GalIV as the main, but not the only, enzyme driving the biosynthesis of SLeX in GI cancer cells, with a functional impact on cancer cell motility.

show abstract

Blood group antigens SLeX, SLeA, and LeY as prognostic markers in endometrial cancer

Cited by 6 publications

References 37 publications

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility

Development and validation of a prognostic nomogram model incorporating routine laboratory biomarkers for preoperative patients with endometrial cancer

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility

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