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Sialyl-Tn identifies muscle-invasive bladder cancer basal and luminal subtypes facing decreased survival, being expressed by circulating tumor cells and metastases

Urologic Oncology: Seminars and Original Investigations Sep 15, 2017

Lima L, et al. - This study was undertaken to investigate the potential of sialyl-Tn (STn), a cancer-associated glycan antigen present in membrane glycoproteins, to enhance a current molecular model for stratification and prognostication of advanced stage bladder tumors based on keratins (KRT14, 5, and 20) expression. This work reinforces the potential of the KRT-based model for bladder cancer management and the association of STn with aggressiveness, supporting its inclusion in predictive molecular models toward patient-tailored precision medicine. Furthermore, analysts present for the first time that circulating tumor cells (CTCs) and the metastasis present a basal phenotype and express the STn antigen, highlighting its link with disease dissemination. Future research should target on determining the biological and clinical significance of these observations in the context of liquid biopsies. Given the membrane nature of STn, highly specific targeted therapeutics may also be envisaged.

Methods
  • Researchers screened a retrospective series of 80 muscle-invasive primary bladder tumors and associated metastasis for KRT14, 5, and 20 and STn by real-time polymerase chain reaction and immunohistochemistry.
  • They collected peripheral blood in a patients’ subset, CTCs were isolated through a size-based microfluidic chip and screened for KRTs and STn.

Results
  • The results showed that basal-like lesions presented worse cancer-specific and disease-free survival compared to luminal tumors.
  • As evidence accumulates, STn antigen inclusion discriminated patients with worst survival in each subgroup (P = 0.047 for luminal; P = 0.027 for basal-like tumors).
  • They further illustrated that STn expression in CTCs and distant metastasis.
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