Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients

Authors: Huyang Xie, Yu Zhu, Junyu Zhang, Zheng Liu, Hangcheng Fu, Yifan Cao, Gaoxiang Li, Yijun Shen, Bo Dai, Jiejie Xu, Dingwei Ye

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

The expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC).

Methods

There were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients’ clinical characteristics, and clinical results.

Results

B4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm2) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression.

Conclusions

Our evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.
Appendix
Available only for authorised users
Literature
1.
2.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRefPubMed
3.
4.
Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–66.CrossRefPubMed
5.
Reardon ZD, Patel SG, Zaid HB, Stimson CJ, Resnick MJ, Keegan KA, Barocas DA, Chang SS, Cookson MS. Trends in the use of perioperative chemotherapy for localized and locally advanced muscle-invasive bladder cancer: a sign of changing tides. Eur Urol. 2015;67(1):165–70.CrossRefPubMed
6.
Leow JJ, Martin-Doyle W, Rajagopal PS, Patel CG, Anderson EM, Rothman AT, Cote RJ, Urun Y, Chang SL, Choueiri TK, et al. Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol. 2014;66(1):42–54.CrossRefPubMed
7.
8.
Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer. 2015;15(9):540–55.CrossRefPubMed
9.
Baras AS, Drake C, Liu JJ, Gandhi N, Kates M, Hoque MO, Meeker A, Hahn N, Taube JM, Schoenberg MP, et al. The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder. Oncoimmunology. 2016;5(5):e1134412.CrossRefPubMedPubMedCentral
10.
Zhou H, Ma H, Wei W, Ji D, Song X, Sun J, Zhang J, Jia L. B4GALT family mediates the multidrug resistance of human leukemia cells by regulating the hedgehog pathway and the expression of p-glycoprotein and multidrug resistance-associated protein 1. Cell Death Dis. 2013;4:e654.CrossRefPubMedPubMedCentral
11.
Shinzaki S, Iijima H, Fujii H, Kuroki E, Tatsunaka N, Inoue T, Nakajima S, Egawa S, Kanto T, Tsujii M, et al. Altered oligosaccharide structures reduce colitis induction in mice defective in beta-1,4-galactosyltransferase. Gastroenterology. 2012;142(5):1172–82.CrossRefPubMed
12.
Choi HJ, Chung TW, Kim CH, Jeong HS, Joo M, Youn B, Ha KT. Estrogen induced beta-1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells. Biochem Biophys Res Commun. 2012;426(4):620–5.CrossRefPubMed
13.
Wei Y, Liu D, Zhou F, Ge Y, Xu J, Yun X, Gu J, Jiang J. Identification of beta-1,4-galactosyltransferase I as a target gene of HBx-induced cell cycle progression of hepatoma cell. J Hepatol. 2008;49(6):1029–37.CrossRefPubMed
14.
Zhu X, Jiang J, Shen H, Wang H, Zong H, Li Z, Yang Y, Niu Z, Liu W, Chen X, et al. Elevated beta1,4-galactosyltransferase I in highly metastatic human lung cancer cells. Identification of E1AF as important transcription activator. J Biol Chem. 2005;280(13):12503–16.CrossRefPubMed
15.
Zhou H, Zhang Z, Liu C, Jin C, Zhang J, Miao X, Jia L. B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562/adriamycin-resistant cell line. IUBMB Life. 2012;64(11):889–900.CrossRefPubMed
16.
Chang HH, Chen CH, Chou CH, Liao YF, Huang MJ, Chen YH, Wang WJ, Huang J, Hung JS, Ho WL, et al. beta-1,4-galactosyltransferase III enhances invasive phenotypes via beta1-integrin and predicts poor prognosis in neuroblastoma. Clin Cancer Res. 2013;19(7):1705–16.CrossRefPubMed
17.
Radhakrishnan P, Chachadi V, Lin MF, Singh R, Kannagi R, Cheng PW. TNFalpha enhances the motility and invasiveness of prostatic cancer cells by stimulating the expression of selective glycosyl- and sulfotransferase genes involved in the synthesis of selectin ligands. Biochem Biophys Res Commun. 2011;409(3):436–41.CrossRefPubMedPubMedCentral
18.
Xie H, Zhu Y, An H, Wang H, Zhu Y, Fu H, Wang Z, Fu Q, Xu J, Ye D. Increased B4GALT1 expression associates with adverse outcome in patients with non-metastatic clear cell renal cell carcinoma. Oncotarget. 2016;7(22):32723–30.PubMedPubMedCentral
19.
Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–7.CrossRefPubMedPubMedCentral
20.
Xu L, Zhu Y, Chen L, An H, Zhang W, Wang G, Lin Z, Xu J. Prognostic value of diametrically polarized tumor-associated macrophages in renal cell carcinoma. Ann Surg Oncol. 2014;21(9):3142–50.CrossRefPubMed
21.
Detre S, Saclani Jotti G, Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995;48(9):876–8.CrossRefPubMedPubMedCentral
22.
Kluth LA, Black PC, Bochner BH, Catto J, Lerner SP, Stenzl A, Sylvester R, Vickers AJ, Xylinas E, Shariat SF. Prognostic and prediction tools in bladder Cancer: a comprehensive review of the literature. Eur Urol. 2015;68(2):238–53.CrossRefPubMed
23.
24.
Witjes JA, Comperat E, Cowan NC, De Santis M, Gakis G, Lebret T, Ribal MJ, Van der Heijden AG, Sherif A, European Association of U. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol. 2014;65(4):778–92.CrossRefPubMed
25.
Galsky MD, Stensland KD, Moshier E, Sfakianos JP, McBride RB, Tsao CK, Casey M, Boffetta P, Oh WK, Mazumdar M, et al. Effectiveness of adjuvant chemotherapy for locally advanced bladder Cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(8):825–32.CrossRef
26.
Rabinovich GA, Toscano MA. Turning ‘sweet’ on immunity: galectin-glycan interactions in immune tolerance and inflammation. Nat Rev Immunol. 2009;9(5):338–52.CrossRefPubMed
27.
28.
29.
Dalgleish AG. Rationale for combining immunotherapy with chemotherapy. Immunotherapy. 2015;7(3):309–16.CrossRefPubMed
Metadata
Title
B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients
Authors
Huyang Xie
Yu Zhu
Junyu Zhang
Zheng Liu
Hangcheng Fu
Yifan Cao
Gaoxiang Li
Yijun Shen
Bo Dai
Jiejie Xu
Dingwei Ye
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4497-0

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

Impact of vitamin D on pathological complete response and survival following neoadjuvant chemotherapy for breast cancer: a retrospective study

Correction

Correction to: Oncology practitioners’ perspectives and practice patterns of post-treatment cancer survivorship care in the Asia-Pacific region: results from the STEP study

Research article

Gut disruption impairs rehabilitation in patients curatively operated for pancreaticoduodenal cancer - a qualitative study

Research article

The presumed MTH1-inhibitor TH588 sensitizes colorectal carcinoma cells to ionizing radiation in hypoxia

Research article

In vitro antineoplastic effects of auranofin in canine lymphoma cells

Research article

Trends in incidence, mortality and survival in women with breast cancer from 1985 to 2012 in Granada, Spain: a population-based study
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits