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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Biomarkers | Research

A sialyltransferases-related gene signature serves as a potential predictor of prognosis and therapeutic response for bladder cancer

Authors: Penglong Cao, Mingying Chen, Tianya Zhang, Qin Zheng, Mulin Liu

Published in: European Journal of Medical Research | Issue 1/2023

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Abstract

Background

Aberrant glycosylation, catalyzed by the specific glycosyltransferase, is one of the dominant features of cancers. Among the glycosyltransferase subfamilies, sialyltransferases (SiaTs) are an essential part which has close linkages with tumor-associated events, such as tumor growth, metastasis and angiogenesis. Considering the relationship between SiaTs and cancer, the current study attempted to establish an effective prognostic model with SiaTs-related genes (SRGs) to predict patients’ outcome and therapeutic responsiveness of bladder cancer.

Methods

RNA-seq data, clinical information and genomic mutation data were downloaded (TCGA-BLCA and GSE13507 datasets). The comprehensive landscape of the 20 SiaTs was analyzed, and the differentially expressed SiaTs-related genes were screened with “DESeq2” R package. ConsensusClusterPlus was applied for clustering, following with survival analysis with Kaplan–Meier curve. The overall survival related SRGs were determined with univariate Cox proportional hazards regression analysis, and the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to generate a SRGs-related prognostic model. The predictive value was estimated with Kaplan–Meier plot and the receiver operating characteristic (ROC) curve, which was further validated with the constructed nomogram and decision curve.

Results

In bladder cancer tissues, 17 out of the 20 SiaTs were differentially expressed with CNV changes and somatic mutations. Two SiaTs_Clusters were determined based on the expression of the 20 SiaTs, and two gene_Clusters were identified based on the expression of differentially expressed genes between SiaTs_Clusters. The SRGs-related prognostic model was generated with 7 key genes (CD109, TEAD4, FN1, TM4SF1, CDCA7L, ATOH8 and GZMA), and the accuracy for outcome prediction was validated with ROC curve and a constructed nomogram. The SRGs-related prognostic signature could separate patients into high- and low-risk group, where the high-risk group showed poorer outcome, more abundant immune infiltration, and higher expression of immune checkpoint genes. In addition, the risk score derived from the SRGs-related prognostic model could be utilized as a predictor to evaluate the responsiveness of patients to the medical therapies.

Conclusions

The SRGs-related prognostic signature could potentially aid in the prediction of the survival outcome and therapy response for patients with bladder cancer, contributing to the development of personalized treatment and appropriate medical decisions.
Literature
1.
Martin A, Woolbright BL, Umar S, Ingersoll MA, Taylor JA 3rd. Bladder cancer, inflammageing and microbiomes. Nat Rev Urol. 2022;19(8):495–509.PubMedCrossRef
2.
3.
Yao J, Liu Y, Yang J, Li M, Li S, Zhang B, et al. Single-Cell sequencing reveals that DBI is the key gene and potential therapeutic target in quiescent bladder cancer stem cells. Front Genet. 2022;3(13): 904536.CrossRef
4.
Lin W, Sun J, Sadahira T, Xu N, Wada K, Liu C, et al. Discovery and validation of nitroxoline as a novel STAT3 inhibitor in drug-resistant urothelial bladder cancer. Int J Biol Sci. 2021;17(12):3255–67.PubMedPubMedCentralCrossRef
5.
Roh YG, Mun JY, Kim SK, Park W, Jeong MS, Kim TN, et al. Fanconi anemia pathway activation by FOXM1 is critical to bladder cancer recurrence and anticancer drug resistance. Cancers (Basel). 2020;12(6):1417.PubMedPubMedCentralCrossRef
6.
Huang J, Su R, Chen Z, Jiang S, Chen M, Yuan Y, et al. The efficacy and safety of first-line treatment in cisplatin-ineligible advanced upper tract urothelial carcinoma patients: a comparison of PD-1 inhibitor and carboplatin plus gemcitabine chemotherapy. Oncoimmunology. 2022;11(1):2124691.PubMedPubMedCentralCrossRef
7.
Wang M, Chen X, Tan P, Wang Y, Pan X, Lin T, et al. Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer. Cancer Cell. 2022;40(9):1044–59.CrossRef
8.
Zhang J, Xun M, Li C, Chen Y. The O-GlcNAcylation and its promotion to hepatocellular carcinoma. Biochim Biophys Acta Rev Cancer. 2022;1877(6): 188806.PubMedCrossRef
9.
Yang S, Cui M, Liu Q, Liao Q. Glycosylation of immunoglobin G in tumors: function, regulation and clinical implications. Cancer Lett. 2022;28(549): 215902.CrossRef
10.
Li J, Guo B, Zhang W, Yue S, Huang S, Gao S, et al. Recent advances in demystifying O-glycosylation in health and disease. Proteomics. 2022;22(23–24): e2200156.CrossRef
11.
Marques C, Poças J, Gomes C, Faria-Ramos I, Reis CA, Vivès RR, et al. Glycosyltransferases EXTL2 and EXTL3 cellular balance dictates Heparan Sulfate biosynthesis and shapes gastric cancer cell motility and invasion. J Biol Chem. 2022;298(11): 102546.PubMedPubMedCentralCrossRef
12.
Liu J, Li M, Wu J, Qi Q, Li Y, Wang S, et al. Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma. Front Immunol. 2022;12(13): 979605.CrossRef
13.
Zhu Q, Zhou H, Wu L, Lai Z, Geng D, Yang W, et al. O-GlcNAcylation promotes pancreatic tumor growth by regulating malate dehydrogenase 1. Nat Chem Biol. 2022;18(10):1087–95.PubMedCrossRef
14.
Wang Q, Liao C, Tan Z, Li X, Guan X, Li H, et al. FUT6 inhibits the proliferation, migration, invasion, and EGF-induced EMT of head and neck squamous cell carcinoma (HNSCC) by regulating EGFR/ERK/STAT signaling pathway. Cancer Gene Ther. 2023;30(1):182–91.PubMedCrossRef
15.
Hu Q, Tian T, Leng Y, Tang Y, Chen S, Lv Y, et al. The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer. Cell Mol Biol Lett. 2022;27(1):71.PubMedCentralCrossRef
16.
Lin S, Zhou L, Dong Y, Yang Q, Yang Q, Jin H, et al. Alpha-(1,6)- fucosyltransferase (FUT8) affects the survival strategy of osteosarcoma by remodeling TNF/NF-κB2 signaling. Cell Death Dis. 2021;12(12):1124.PubMedPubMedCentralCrossRef
17.
Mabe NW, Huang M, Dalton GN, Alexe G, Schaefer DA, Geraghty AC, et al. Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1. Nat Cancer. 2022;3(8):976–93.PubMedPubMedCentralCrossRef
18.
Kvorjak M, Ahmed Y, Miller ML, Sriram R, Coronnello C, Hashash JG, et al. Cross-talk between colon cells and macrophages increases ST6GALNAC1 and MUC1-sTn expression in ulcerative colitis and colitis-associated colon cancer. Cancer Immunol Res. 2020;8(2):167–78.PubMedCrossRef
19.
Pietrobono S, Anichini G, Sala C, Manetti F, Almada LL, Pepe S, et al. ST3GAL1 is a target of the SOX2-GLI1 transcriptional complex and promotes melanoma metastasis through AXL. Nat Commun. 2020;11(1):5865.PubMedPubMedCentralCrossRef
20.
Guerrero PE, Miró L, Wong BS, Massaguer A, Martínez-Bosch N, Llorens R, et al. Knockdown of α2,3-sialyltransferases impairs pancreatic cancer cell migration, invasion and e-selectin-dependent adhesion. Int J Mol Sci. 2020;21(17):6239.PubMedPubMedCentralCrossRef
21.
Hait NC, Maiti A, Wu R, Andersen VL, Hsu CC, Wu Y, et al. Extracellular sialyltransferase st6gal1 in breast tumor cell growth and invasiveness. Cancer Gene Ther. 2022;29(11):1662–75.PubMedCrossRef
22.
Hao J, Zeltz C, Pintilie M, Li Q, Sakashita S, Wang T, et al. Characterization of distinct populations of carcinoma-associated fibroblasts from non-small cell lung carcinoma reveals a role for ST8SIA2 in cancer cell invasion. Neoplasia. 2019;21(5):482–93.PubMedPubMedCentralCrossRef
23.
Liu R, Cao X, Liang Y, Li X, Jin Q, Li Y, et al. Downregulation of ST6GAL1 promotes liver inflammation and predicts adverse prognosis in hepatocellular carcinoma. J Inflamm Res. 2022;10(15):5801–14.CrossRef
24.
Wang WY, Cao YX, Zhou X, Wei B, Zhan L, Sun SY. Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway. Cancer Cell Int. 2019;5(19):86.CrossRef
25.
Scott E, Archer Goode E, Garnham R, Hodgson K, Orozco-Moreno M, Turner H, et al. ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression. J Pathol. 2023;261(1):71–84.PubMedCrossRef
26.
di Meo NA, Lasorsa F, Rutigliano M, Milella M, Ferro M, Battaglia M, et al. The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery. Expert Rev Mol Diagn. 2023;23(4):297–313.CrossRef
27.
Lasorsa F, di Meo NA, Rutigliano M, Ferro M, Terracciano D, Tataru OS, et al. Emerging hallmarks of metabolic reprogramming in prostate cancer. Int J Mol Sci. 2023;24(2):910.PubMedPubMedCentralCrossRef
28.
Lucarelli G, Loizzo D, Ferro M, Rutigliano M, Vartolomei MD, Cantiello F, et al. Metabolomic profiling for the identification of novel diagnostic markers and therapeutic targets in prostate cancer: an update. Expert Rev Mol Diagn. 2019;19(5):377–87.PubMedCrossRef
29.
di Meo NA, Lasorsa F, Rutigliano M, Loizzo D, Ferro M, Stella A, et al. Renal cell carcinoma as a metabolic disease: an update on main pathways, potential biomarkers, and therapeutic targets. Int J Mol Sci. 2022;23(22):14360.PubMedPubMedCentralCrossRef
30.
Lucarelli G, Loizzo D, Franzin R, Battaglia S, Ferro M, Cantiello F, et al. Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma. Expert Rev Mol Diagn. 2019;19(5):397–407.PubMedCrossRef
31.
di Meo NA, Loizzo D, Pandolfo SD, Autorino R, Ferro M, Porta C, et al. Metabolomic approaches for detection and identification of biomarkers and altered pathways in bladder cancer. Int J Mol Sci. 2022;23(8):4173.PubMedCrossRef
32.
Sahu D, Lotan Y, Wittmann B, Neri B, Hansel DE. Metabolomics analysis reveals distinct profiles of nonmuscle-invasive and muscle-invasive bladder cancer. Cancer Med. 2017;6(9):2106–20.PubMedPubMedCentralCrossRef
33.
Aveta A, Cilio S, Contieri R, Spena G, Napolitano L, Manfredi C, et al. Urinary MicroRNAs as biomarkers of urological cancers: a systematic review. Int J Mol Sci. 2023;24(13):10846.PubMedPubMedCentralCrossRef
34.
Ferro M, Crocetto F, Tataru S, Barone B, Dolce P, Lucarelli G, et al. Predictors of efficacy of immune checkpoint inhibitors in patients with advanced urothelial carcinoma: a systematic review and meta-analysis. Clin Genitourin Cancer. 2023;21(5):574–83.PubMedCrossRef
35.
Barone B, Calogero A, Scafuri L, Ferro M, Lucarelli G, Di Zazzo E, et al. Immune checkpoint inhibitors as a neoadjuvant/adjuvant treatment of muscle-invasive bladder cancer: a systematic review. Cancers (Basel). 2022;14(10):2545.PubMedCrossRef
36.
Ferro M, La Civita E, Liotti A, Cennamo M, Tortora F, Buonerba C, et al. Liquid biopsy biomarkers in urine: a route towards molecular diagnosis and personalized medicine of bladder cancer. J Pers Med. 2021;11(3):237.PubMedPubMedCentralCrossRef
37.
Pan S, Li S, Zhan Y, Chen X, Sun M, Liu X, et al. Immune status for monitoring and treatment of bladder cancer. Front Immunol. 2022;8(13): 963877.CrossRef
38.
Biswas PK, Kwak Y, Kim A, Seok J, Kwak HJ, Lee M, et al. TTYH3 modulates bladder cancer proliferation and metastasis via FGFR1/H-Ras/A-Raf/MEK/ERK pathway. Int J Mol Sci. 2022;23(18):10496.PubMedPubMedCentralCrossRef
39.
Chow PM, Dong JR, Chang YW, Kuo KL, Lin WC, Liu SH, et al. The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma. Mol Ther Oncolytics. 2022;5(26):387–98.CrossRef
40.
Wang L, Chen X, Wang L, Wang S, Li W, Liu Y, et al. Knockdown of ST6Gal-I expression in human hepatocellular carcinoma cells inhibits their exosome-mediated proliferation- and migration-promoting effects. IUBMB Life. 2021;73(11):1378–91.PubMedCrossRef
41.
Nguyen K, Yan Y, Yuan B, Dasgupta A, Sun J, Mu H, et al. ST8SIA1 regulates tumor growth and metastasis in TNBC by activating the FAK-AKT-mTOR signaling pathway. Mol Cancer Ther. 2018;17(12):2689–701.PubMedCrossRef
42.
Yeo HL, Fan TC, Lin RJ, Yu JC, Liao GS, Chen ES, et al. Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression. Int J Cancer. 2019;144(8):1996–2007.PubMedPubMedCentralCrossRef
43.
Ma H, Zhou H, Song X, Shi S, Zhang J, Jia L. Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia. Oncogene. 2015;34(6):726–40.PubMedCrossRef
44.
Zhang W, Li J, Wu Y, Ge H, Song Y, Wang D, et al. TEAD4 overexpression promotes epithelial-mesenchymal transition and associates with aggressiveness and adverse prognosis in head neck squamous cell carcinoma. Cancer Cell Int. 2018;12(18):178.CrossRef
45.
Cozzaglio M, Ceschi S, Groaz E, Sturlese M, Sissi C. G-quadruplexes formation within the promoter of TEAD4 oncogene and their interaction with Vimentin. Front Chem. 2022;15(10):1008075.CrossRef
46.
Zhang Y, Bai J, Cheng R, Zhang D, Qiu Z, Liu T, et al. TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4. J Gastroenterol Hepatol. 2022;37(4):714–26.PubMedCrossRef
47.
He L, Yuan L, Sun Y, Wang P, Zhang H, Feng X, et al. Glucocorticoid receptor signaling activates TEAD4 to promote breast cancer progression. Cancer Res. 2019;79(17):4399–411.PubMedCrossRef
48.
Chi M, Liu J, Mei C, Shi Y, Liu N, Jiang X, et al. TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K/AKT pathway in bladder cancer. J Exp Clin Cancer Res. 2022;41(1):175.PubMedPubMedCentralCrossRef
49.
Wang J, Shen C, Zhang J, Zhang Y, Liang Z, Niu H, et al. TEAD4 is an immune regulating-related prognostic biomarker for bladder cancer and possesses generalization value in pan-cancer. DNA Cell Biol. 2021;40(6):798–810.PubMedCrossRef
50.
Divvela SSK, Saberi D, Brand-Saberi B. Atoh8 in development and disease. Biology (Basel). 2022;11(1):136.PubMed
51.
Xu M, Huang S, Dong X, Chen Y, Li M, Shi W, et al. A novel isoform of ATOH8 promotes the metastasis of breast cancer by regulating RhoC. J Mol Cell Biol. 2021;13(1):59–71.PubMedCrossRef
52.
Song Y, Pan G, Chen L, Ma S, Zeng T, Man Chan TH, et al. Loss of ATOH8 increases stem cell features of hepatocellular carcinoma cells. Gastroenterology. 2015;149(4):1068–81.PubMedCrossRef
53.
Hu X, Yang Y, Wang Y, Ren S, Li X. Identifying an immune-related gene ST8SIA1 as a novel target in patients with clear-cell renal cell carcinoma. Front Pharmacol. 2022;7(13): 901518.CrossRef
54.
Ko CY, Chu TH, Hsu CC, Chen HP, Huang SC, Chang CL, et al. Bioinformatics analyses identify the therapeutic potential of ST8SIA6 for colon cancer. J Pers Med. 2022;12(3):401.PubMedPubMedCentralCrossRef
55.
Yang M, Wang B, Hou W, Yu H, Zhou B, Zhong W, et al. Negative effects of stromal neutrophils on T cells reduce survival in resectable urothelial carcinoma of the bladder. Front Immunol. 2022;21(13): 827457.CrossRef
56.
Tang Z, Tang C, Sun C, Ying X, Shen R. M1 macrophage-derived exosomes synergistically enhance the anti- bladder cancer effect of gemcitabine. Aging (Albany NY). 2022;14(18):7364–77.PubMedCrossRef
57.
Chiang Y, Tsai YC, Wang CC, Hsueh FJ, Huang CY, Chung SD, et al. Tumor-Derived C-C motif ligand 2 induces the recruitment and polarization of tumor-associated macrophages and increases the metastatic potential of bladder cancer cells in the postirradiated microenvironment. Int J Radiat Oncol Biol Phys. 2022;114(2):321–33.PubMedCrossRef
58.
Jin S, Zeng H, Liu Z, Jin K, Liu C, Yan S, et al. Stromal tumor-associated macrophage infiltration predicts poor clinical outcomes in muscle-invasive bladder cancer patients. Ann Surg Oncol. 2022;29(4):2495–503.PubMedCrossRef
59.
Liu Z, Zhu Y, Xu L, Zhang J, Xie H, Fu H, et al. Tumor stroma-infiltrating mast cells predict prognosis and adjuvant chemotherapeutic benefits in patients with muscle invasive bladder cancer. Oncoimmunology. 2018;7(9): e1474317.PubMedPubMedCentralCrossRef
Metadata
Title
A sialyltransferases-related gene signature serves as a potential predictor of prognosis and therapeutic response for bladder cancer
Authors
Penglong Cao
Mingying Chen
Tianya Zhang
Qin Zheng
Mulin Liu
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Biomarkers
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01496-7

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