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The B4GALT1 expression is prognostic and predictive for postoperative adjuvant chemotherapy benefit in patients with muscle-invasive bladder cancer

Login to Access Video or Poster Abstract: MP58-08
Sources of Funding: This study was funded by grants from National Natural Science Foundation of China (81472377, 81572531)

Introduction

Beta-1, 4-Galactosyltransferase gene (B4GALT) family consists of seven members, which encode corresponding enzymes known as type II membrane-bound glycoproteins. These enzymes catalyze the biosynthesis of different glycoconjugates and saccharide structures, and have been recognized to be involved in various diseases. In this study, we sought to determine the bladder cancer cell's B4GALT1 expression and its association with the infiltrated CD8+ T cell number, together with the association with the patients’ outcome, as well as the benefit from adjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC).

Methods

We recruited 201 and 172 patients consecutively with bladder cancer treated by radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. The first cohort with 201 patients was treated as training set and the other as validation set. TMAs were created in triplicated from formalin-fixed, paraffin embedded specimens. Immunohistochemistry was performed to assess the expression of B4GALT1 in tumor cores and CD8 in both tumor and peri-tumor cores, and its association between B4GALT1 and the infiltrated CD8+ T cell number, also with clinical outcomes.

Results

B4GALT1 expression was significantly associated with tumor size (P=0.005 and P=0.014, respectively), T stage (P=0.017 and P=0.004, respectively), OS (P<0.001 and P<0.001, respectively) and PFS (P=0.033 and P=0.034, respectively) in both cohorts. Furthermore, high expression of B4GALT1 was an independent indicator of poor OS (P=0.022 and P=0.017, respectively) in patients with MIBC. The prognostic model containing B4GALT1 showed a better predictive accuracy than the basic models. And the B4GALT1 expression was inverse correlated with the number of peri-tumor infiltrated CD8+ T cell, but not with the number of tumor infiltrated CD8+ T cell. Most importantly, the benefit of adjuvant chemotherapy observed in non-organ confined bladder cancer patients with low B4GALT1 expression was superior to patients with high expression.

Conclusions

Our study suggested that B4GALT1 is a potential prognostic biomarker of MIBC, and might be a predictive marker for the patients’ selection of adjuvant chemotherapy in high recurrence risk subgroup patients.

Funding

This study was funded by grants from National Natural Science Foundation of China (81472377, 81572531)

Authors
Huyang Xie
Yu Zhu
Zewei Wang
Qiang Fu
Jiejie Xu
Dingwei Ye
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