4.6
CiteScore
2.2
Impact Factor
- ISSN 1674-8301
- CN 32-1810/R
4.6
2.2
| Citation: |
Mengfan Guo, Jingyuan Liu, Yujuan Zhang, Jingjing Gu, Junyi Xin, Mulong Du, Haiyan Chu, Meilin Wang, Hanting Liu, Zhengdong Zhang. Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration[J]. The Journal of Biomedical Research, 2024, 38(4): 348-357. DOI: 10.7555/JBR.37.20230161
|
Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1GALT1) is known to play a critical role in the development of gastric cancer, but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk. By using the genome-wide association study data from the database of Genotype and Phenotype (dbGAP), we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk (odds ratio, 0.83; 95% confidence interval [CI], 0.75–0.92; P = 3.95 × 10−4). C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues, and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates (hazards ratio, 1.33; 95% CI, 1.05–1.68; Plog-rank = 1.90 × 10−2). Furthermore, we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4+ T cells and macrophages. These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.
The present study was funded by the National Key R&D Program of China (Grant Nos. 2018YFC1313100 and 2018YFC1313102), the National Natural Science Foundation of China (Grant No. 81773539), Collaborative Innovation Center for Cancer Personalized Medicine, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).
The authors would like to thank Dr. Xudong Song of the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University for providing assistance with sample collection.
CLC number: R735.2, Document code: A
The authors reported no conflict of interests.
| [1] |
Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J (Engl), 2022, 135(5): 584–590. doi: 10.1097/CM9.0000000000002108
|
| [2] |
Plummer M, Franceschi S, Vignat J, et al. Global burden of gastric cancer attributable to Helicobacter pylori[J]. Int J Cancer, 2015, 136(2): 487–490. doi: 10.1002/ijc.28999
|
| [3] |
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394–424. doi: 10.3322/caac.21492
|
| [4] |
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115–132. doi: 10.3322/caac.21338
|
| [5] |
Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer[J]. Lancet, 2020, 396(10251): 635–648. doi: 10.1016/S0140-6736(20)31288-5
|
| [6] |
The International HapMap Consortium. A haplotype map of the human genome[J]. Nature, 2005, 437(7063): 1299–1320. doi: 10.1038/nature04226
|
| [7] |
Xu M, Qiang F, Gao Y, et al. Evaluation of a novel functional single-nucleotide polymorphism (rs35010275 G>C) in MIR196A2 promoter region as a risk factor of gastric cancer in a Chinese population[J]. Medicine (Baltimore), 2014, 93(26): e173. doi: 10.1097/MD.0000000000000173
|
| [8] |
Yan C, Zhu M, Ding Y, et al. Meta-analysis of genome-wide association studies and functional assays decipher susceptibility genes for gastric cancer in Chinese populations[J]. Gut, 2020, 69(4): 641–651. doi: 10.1136/gutjnl-2019-318760
|
| [9] |
Munkley J, Elliott DJ. Hallmarks of glycosylation in cancer[J]. Oncotarget, 2016, 7(23): 35478–35489. doi: 10.18632/oncotarget.8155
|
| [10] |
Peixoto A, Relvas-Santos M, Azevedo R, et al. Protein glycosylation and tumor microenvironment alterations driving cancer hallmarks[J]. Front Oncol, 2019, 9: 380. doi: 10.3389/fonc.2019.00380
|
| [11] |
Martinez-Morales P, Morán Cruz I, Roa-de la Cruz L, et al. Hallmarks of glycogene expression and glycosylation pathways in squamous and adenocarcinoma cervical cancer[J]. PeerJ, 2021, 9: e12081. doi: 10.7717/peerj.12081
|
| [12] |
Silsirivanit A. Glycosylation markers in cancer[J]. Adv Clin Chem, 2019, 89: 189–213. doi: 10.1016/bs.acc.2018.12.005
|
| [13] |
Magalhães A, Duarte HO, Reis CA. The role of O-glycosylation in human disease[J]. Mol Aspects Med, 2021, 79: 100964. doi: 10.1016/j.mam.2021.100964
|
| [14] |
Bennett EP, Mandel U, Clausen H, et al. Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family[J]. Glycobiology, 2012, 22(6): 736–756. doi: 10.1093/glycob/cwr182
|
| [15] |
Chugh S, Barkeer S, Rachagani S, et al. Disruption of C1galt1 gene promotes development and metastasis of pancreatic adenocarcinomas in mice[J]. Gastroenterology, 2018, 155(5): 1608–1624. doi: 10.1053/j.gastro.2018.08.007
|
| [16] |
Liu F, Fu J, Bergstrom K, et al. Core 1-derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer[J]. J Exp Med, 2020, 217(1): e20182325. doi: 10.1084/jem.20182325
|
| [17] |
Dong X, Chen C, Deng X, et al. A novel mechanism for C1GALT1 in the regulation of gastric cancer progression[J]. Cell Biosci, 2021, 11(1): 166. doi: 10.1186/s13578-021-00678-2
|
| [18] |
Sun X, Zhan M, Sun X, et al. C1GALT1 in health and disease (Review)[J]. Oncol Lett, 2021, 22(2): 589. doi: 10.3892/ol.2021.12850
|
| [19] |
Kim R, An M, Lee H, et al. Early tumor-immune microenvironmental remodeling and response to first-line fluoropyrimidine and platinum chemotherapy in advanced gastric cancer[J]. Cancer Discov, 2022, 12(4): 984–1001. doi: 10.1158/2159-8290.CD-21-0888
|
| [20] |
Wang Y, Zhou X, Chen P, et al. Interaction between GALNT12 and C1GALT1 associates with galactose-deficient IgA1 and IgA nephropathy[J]. J Am Soc Nephrol, 2021, 32(3): 545–552. doi: 10.1681/ASN.2020060823
|
| [21] |
Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies[J]. PLoS Genet, 2009, 5(6): e1000529. doi: 10.1371/journal.pgen.1000529
|
| [22] |
Elsworth B, Lyon M, Alexander T, et al. The MRC IEU OpenGWAS data infrastructure[EB/OL]. [2022-11-12]. https://doi.org/10.1101/2020.08.10.244293.
|
| [23] |
Pontén F, Jirström K, Uhlen M. The Human Protein Atlas—a tool for pathology[J]. J Pathol, 2008, 216(4): 387–393. doi: 10.1002/path.2440
|
| [24] |
Li T, Fan J, Wang B, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells[J]. Cancer Res, 2017, 77(21): e108–e110. doi: 10.1158/0008-5472.CAN-17-0307
|
| [25] |
Tan Z, Jiang Y, Liang L, et al. Dysregulation and prometastatic function of glycosyltransferase C1GALT1 modulated by cHP1BP3/ miR-1-3p axis in bladder cancer[J]. J Exp Clin Cancer Res, 2022, 41(1): 228. doi: 10.1186/s13046-022-02438-7
|
| [26] |
Lee PC, Chen ST, Kuo TC, et al. C1GALT1 is associated with poor survival and promotes soluble Ephrin A1-mediated cell migration through activation of EPHA2 in gastric cancer[J]. Oncogene, 2020, 39(13): 2724–2740. doi: 10.1038/s41388-020-1178-7
|
| [27] |
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process—first American cancer society award lecture on cancer epidemiology and prevention[J]. Cancer Res, 1992, 52(24): 6735–6740. https://europepmc.org/article/MED/1458460
|
| [28] |
McGuckin MA, Lindén SK, Sutton P, et al. Mucin dynamics and enteric pathogens[J]. Nat Rev Microbiol, 2011, 9(4): 265–278. doi: 10.1038/nrmicro2538
|
| [29] |
Magalhães A, Rossez Y, Robbe-Masselot C, et al. Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding[J]. Sci Rep, 2016, 6: 25575. doi: 10.1038/srep25575
|
| [30] |
Zhang H, Fu L. The role of ALDH2 in tumorigenesis and tumor progression: targeting ALDH2 as a potential cancer treatment[J]. Acta Pharm Sin B, 2021, 11(6): 1400–1411. doi: 10.1016/j.apsb.2021.02.008
|
| [31] |
Kuo T, Wu MH, Yang SH, et al. C1GALT1 high expression is associated with poor survival of patients with pancreatic ductal adenocarcinoma and promotes cell invasiveness through integrin αv[J]. Oncogene, 2021, 40(7): 1242–1254. doi: 10.1038/s41388-020-01594-4
|
| [32] |
Wu Y, Liu CH, Huang MJ, et al. C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization[J]. Cancer Res, 2013, 73(17): 5580–5590. doi: 10.1158/0008-5472.CAN-13-0869
|
| [33] |
Alexander WS, Viney EM, Zhang J, et al. Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene[J]. Proc Natl Acad Sci U S A, 2006, 103(44): 16442–16447. doi: 10.1073/pnas.0607872103
|
| [34] |
Lin M, Chuang Y, Wu HY, et al. Targeting tumor O-glycosylation modulates cancer-immune-cell crosstalk and enhances anti-PD-1 immunotherapy in head and neck cancer[J]. Mol Oncol, 2024, 18(2): 350–368. doi: 10.1002/1878-0261.13489.[Epubaheadofprint
|
| [1] | Tiwari-Heckler Shilpa, Jiang Z. Gordon, Popov Yury, J. Mukamal Kenneth. Daily high-dose aspirin does not lower APRI in the Aspirin-Myocardial Infarction Study[J]. The Journal of Biomedical Research, 2020, 34(2): 139-142. DOI: 10.7555/JBR.33.20190041 |
| [2] | Tao Chun'ai, Gan Yongxin, Su Weidong, Li Zhutian, Tang Xiaolan. Effectiveness of hospital disinfection and experience learnt from 11 years of surveillance[J]. The Journal of Biomedical Research, 2019, 33(6): 408-413. DOI: 10.7555/JBR.33.20180118 |
| [3] | Huan Liu, Shijiang Zhang, Yongfeng Shao, Xiaohu Lu, Weidong Gu, Buqing Ni, Qun Gu, Junjie Du. Biomechanical characterization of a novel ring connector for sutureless aortic anastomosis[J]. The Journal of Biomedical Research, 2018, 32(6): 454-460. DOI: 10.7555/JBR.31.20170011 |
| [4] | Minbo Zang, Qiao Zhou, Yunfei Zhu, Mingxi Liu, Zuomin Zhou. Effects of chemotherapeutic agent bendamustine for nonhodgkin lymphoma on spermatogenesis in mice[J]. The Journal of Biomedical Research, 2018, 32(6): 442-453. DOI: 10.7555/JBR.31.20170023 |
| [5] | Kaibo Lin, Shikun Zhang, Jieli Chen, Ding Yang, Mengyi Zhu, Eugene Yujun Xu. Generation and functional characterization of a conditional Pumilio2 null allele[J]. The Journal of Biomedical Research, 2018, 32(6): 434-441. DOI: 10.7555/JBR.32.20170117 |
| [6] | Huanqiang Wang, Congying Yang, Siyuan Wang, Tian Wang, Jingling Han, Kai Wei, Fucun Liu, Jida Xu, Xianzhen Peng, Jianming Wang. Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer[J]. The Journal of Biomedical Research, 2018, 32(6): 424-433. DOI: 10.7555/JBR.32.20170065 |
| [7] | Fengzhen Wang, Mingwan Zhang, Dongsheng Zhang, Yuan Huang, Li Chen, Sunmin Jiang, Kun Shi, Rui Li. Preparation, optimization, and characterization of chitosancoated solid lipid nanoparticles for ocular drug delivery[J]. The Journal of Biomedical Research, 2018, 32(6): 411-423. DOI: 10.7555/JBR.32.20160170 |
| [8] | Christopher J. Danford, Zemin Yao, Z. Gordon Jiang. Non-alcoholic fatty liver disease: a narrative review of genetics[J]. The Journal of Biomedical Research, 2018, 32(6): 389-400. DOI: 10.7555/JBR.32.20180045 |
| [9] | Yong Ji, Mingfeng Zheng, Shugao Ye, Jingyu Chen, Yijiang Chen. PTEN and Ki67 expression is associated with clinicopathologic features of non-small cell lung cancer[J]. The Journal of Biomedical Research, 2014, 28(6): 462-467. DOI: 10.7555/JBR.27.20130084 |
| [10] | Xiaodong Yang, Ping Huang, Feng Wang, Zekuan Xu, Xiaonin Wang. Growth hormone receptor expression in human primary gastric adenocarcinoma[J]. The Journal of Biomedical Research, 2012, 26(5): 307-314. DOI: 10.7555/JBR.26.20110133 |
| 1. | Tazesh S, Tamizi E, Siahi Shadbad M, et al. Comparative Stability of Two Anti-hyperpigmentation Agents: Kojic Acid as a Natural Metabolite and Its Di-Palmitate Ester, Under Oxidative Stress; Application to Pharmaceutical Formulation Design. Adv Pharm Bull, 2022, 12(2): 329-335. DOI:10.34172/apb.2022.031 |
Figures(4) / Tables(2)
Supported by: Beijing Renhe Information Technology Co., Ltd. E-mail:
info@rhhz.net 
Authors and Reviewers
DownLoad: