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胃癌预后全基因组关联分析

任南 吕雪洁 何陈周 康淑玲 李沛欣 颜伟 刘宝英 吕燕萍 吴传城

任南, 吕雪洁, 何陈周, 康淑玲, 李沛欣, 颜伟, 刘宝英, 吕燕萍, 吴传城. 胃癌预后全基因组关联分析[J]. 中国公共卫生, 2023, 39(2): 151-157. doi: 10.11847/zgggws1138728
引用本文: 任南, 吕雪洁, 何陈周, 康淑玲, 李沛欣, 颜伟, 刘宝英, 吕燕萍, 吴传城. 胃癌预后全基因组关联分析[J]. 中国公共卫生, 2023, 39(2): 151-157. doi: 10.11847/zgggws1138728
REN Nan, LÜ Xue-jie, HE Chen-zhou, LÜ Yan-ping, . Gastric cancer prognosis-related single nucleotide polymorphisms: a genome-wide association analysis[J]. Chinese Journal of Public Health, 2023, 39(2): 151-157. doi: 10.11847/zgggws1138728
Citation: REN Nan, LÜ Xue-jie, HE Chen-zhou, LÜ Yan-ping, . Gastric cancer prognosis-related single nucleotide polymorphisms: a genome-wide association analysis[J]. Chinese Journal of Public Health, 2023, 39(2): 151-157. doi: 10.11847/zgggws1138728

胃癌预后全基因组关联分析

doi: 10.11847/zgggws1138728
基金项目: 福建省自然科学基金(2015J01673;2017J01811);福建省仙游县消化道肿瘤病因学、流行病学研究项目(NO.2013B008)
详细信息
    作者简介:

    任南(1976 – ),女,福建福州人, 实验师,硕士,研究方向:肿瘤分子流行病学

    通信作者:

    吕燕萍,E-mail:LYP0094@163.com

    吴传城,E-mail:wcc@fjmu.edu.cn

  • 中图分类号: R 735.2

Gastric cancer prognosis-related single nucleotide polymorphisms: a genome-wide association analysis

  • 摘要:   目的   探讨胃癌预后相关的全基因组单核苷酸多态性(SNPs)位点,为识别胃癌预后生物标志物、开发个性化胃癌治疗策略提供新的思路。  方法  对2013年4月 — 2017年12月在福建省仙游县医院新确诊的251例胃癌患者进行随访研究,采用Kaplan-Meier法计算5年生存率,通过全基因组芯片检测胃癌患者的全基因组SNPs位点,并应用Cox比例风险回归模型探索胃癌预后相关的SNPs位点。  结果  有效随访胃癌患者218例,随访率为86.85 %,1、3、5年生存率分别为61.5 %、40.8 %、37.5 %,中位生存期为22.0个月;单因素Cox比例风险回归模型分析结果显示,年龄 $\, \geqslant\,$ 65岁、TNM分期中期和晚期是胃癌预后不良的危险因素,接受手术治疗和化疗治疗为胃癌预后不良的保护因素;胃癌预后的全基因组关联分析(GWAS)发现165个与胃癌预后存在全基因组显著性关联的遗传位点,涉及33个功能区域,对应55个功能基因,主要参与生长因子反应通路、免疫逃逸、炎性相关通路等生物过程,其中7个基因的表达在TCGA数据库中显示与胃癌预后显著相关。  结论  SNPs与胃癌预后紧密相关,胃癌预后功能基因广泛参与癌细胞增殖、免疫、炎症等生物过程。
  • 图  1  胃癌预后的GWAS研究Q-Q图和曼哈顿图

    图  2  SNPs密度分布图

    图  3  胃癌生存相关基因GO和KEGG富集分析柱状图和气泡图

    图  4  胃癌生存相关基因与其预后的生存曲线图

    注:蓝色为基因低表达组,红色为基因高表达组。

    表  1  不同特征胃癌患者5年生存率比较

    特征调查例数5年生存率(%)χ2P
    性别 男性 162 37.49 0.249 0.617
    女性 56 37.50
    年龄(岁) < 65 45 51.11 4.093 0.043
    $\geqslant $ 65 173 33.97
    TNM分期 早期 41 87.80 146.949 < 0.001
    中期 74 53.40
    晚期 103 5.83
    是否接受手术治疗 78 16.67 40.598 < 0.001
    140 49.06
    是否接受化疗治疗 102 30.39 7.342 0.007
    116 43.76
    是否接受放疗治疗 189 36.34 0.650 0.420
    29 44.83
    肿瘤位置 非贲门 71 46.48 1.768 0.184
    贲门 147 33.10
    下载: 导出CSV
  • [1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2021, 71(3): 209 – 249. doi: 10.3322/caac.21660
    [2] 曹毛毛, 李贺, 孙殿钦, 等. 2000 — 2019年中国胃癌流行病学趋势分析[J]. 中华消化外科杂志, 2021, 20(1): 102 – 109. doi: 10.3760/cma.j.cn115610-20201130-00746
    [3] 郭佳, 贺媛, 王学梅, 等. 中国居民1990年与2017年胃癌疾病负担比较[J]. 中国公共卫生, 2022, 38(5): 547 – 552. doi: 10.11847/zgggws1134352
    [4] Jin GF, Lv J, Yang M, et al. Genetic risk, incident gastric cancer, and healthy lifestyle: a meta - analysis of genome - wide association studies and prospective cohort study[J]. The Lancet Oncology, 2020, 21(10): 1378 – 1386. doi: 10.1016/S1470-2045(20)30460-5
    [5] 沈超, 姚敏, 尹荣, 等. KIR3DL1 rs35974949和rs35656676位点基因多态性与HCV易感性和慢性化关系[J]. 中国公共卫生, 2022, 38(7): 852 – 855. doi: 10.11847/zgggws1135392
    [6] Wang MH, Cordell HJ, Van Steen K. Statistical methods for genome - wide association studies[J]. Seminars in Cancer Biology, 2019, 55: 53 – 60. doi: 10.1016/j.semcancer.2018.04.008
    [7] Yan CW, Zhu M, Ding YB, 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
    [8] Badr MT, Omar M, Häcker G. Comprehensive integration of genome - wide association and gene expression studies reveals novel gene signatures and potential therapeutic targets for Helicobacter pylori - induced gastric disease[J]. Frontiers in Immunology, 2021, 12: 624117. doi: 10.3389/fimmu.2021.624117
    [9] Chen KX, Yang D, Li XC, et al. Mutational landscape of gastric adenocarcinoma in Chinese: implications for prognosis and therapy[J]. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(4): 1107 – 1112. doi: 10.1073/pnas.1422640112
    [10] Udagawa C, Sasaki Y, Tanizawa Y, et al. Whole - exome sequenc-ing of 79 xenografts as a potential approach for the identification of genetic variants associated with sensitivity to cytotoxic anticancer drugs[J]. PLoS One, 2020, 15(9): e0239614. doi: 10.1371/journal.pone.0239614
    [11] Zhang J, Huang JY, Chen YN, et al. Whole genome and transcri-ptome sequencing of matched primary and peritoneal metastatic gastric carcinoma[J]. Scientific Reports, 2015, 5(1): 13750. doi: 10.1038/srep13750
    [12] 倪婧. 遗传变异与胃癌预后全基因组关联研究[D]. 南京: 南京医科大学, 2020.
    [13] Das S, Forer L, Schönherr S, et al. Next - generation genotype imputation service and methods[J]. Nature Genetics, 2016, 48(10): 1284 – 1287. doi: 10.1038/ng.3656
    [14] Wang K, Li M Y, Hakonarson H. ANNOVAR: functional annota-tion of genetic variants from high - throughput sequencing data[J]. Nucleic Acids Research, 2010, 38(16): e164. doi: 10.1093/nar/gkq603
    [15] Wang C, Shang CZ, Gai XH, et al. Sulfatase 2 - induced cancer - associated fibroblasts promote hepatocellular carcinoma progres-sion via inhibition of apoptosis and induction of epithelial - to - mesenchymal transition[J]. Frontiers in Cell and Developmental Biology, 2021, 9: 631931. doi: 10.3389/fcell.2021.631931
    [16] Jiang T, Chen ZH, Chen Z, et al. SULF2 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells through the ERK/AKT signaling pathway[J]. Brazilian Journal of Medical and Biological Research, 2020, 53(2): e8901. doi: 10.1590/1414-431x20198901
    [17] Huang JH, Li C, Zhang WT, et al. SULF2 is a novel diagnostic and prognostic marker for high - grade bladder cancer with lymphatic metastasis[J]. Annals of Translational Medicine, 2021, 9(18): 1439. doi: 10.21037/atm-21-4102
    [18] Lui NS, Yang YW, Van Zante A, et al. SULF2 expression is a potential diagnostic and prognostic marker in lung cancer[J]. PLoS One, 2016, 11(2): e0148911. doi: 10.1371/journal.pone.0148911
    [19] Wang L, Xie L, Wang J, et al. Correlation between the methylation of SULF2 and WRN promoter and the irinotecan chemosensitivity in gastric cancer[J]. BMC Gastroenterology, 2013, 13(1): 173. doi: 10.1186/1471-230X-13-173
    [20] Hur K, Han TS, Jung EJ, et al. Up - regulated expression of sulfa-tases (SULF1 and SULF2) as prognostic and metastasis predictive markers in human gastric cancer[J]. The Journal of Pathology, 2012, 228(1): 88 – 98. doi: 10.1002/path.4055
    [21] Shao SJ, Piao LH, Guo LW, et al. Tetraspanin 7 promotes osteo-sarcoma cell invasion and metastasis by inducing EMT and activating the FAK - Src - Ras - ERK1/2 signaling pathway[J]. Cancer Cell International, 2022, 22(1): 183. doi: 10.1186/s12935-022-02591-1
    [22] Liu YJ, Yin SY, Zeng SH, et al. Prognostic value of LHFPL tetraspan subfamily member 6 (LHFPL6) in gastric cancer: a study based on bioinformatics analysis and experimental valida-tion[J]. Pharmacogenomics and Personalized Medicine, 2021, 14: 1483 – 1504. doi: 10.2147/PGPM.S332345
    [23] Zhao QY, Zhao RL, Song CH, et al. Increased IGFBP7 expression correlates with poor prognosis and immune infiltration in gastric cancer[J]. Journal of Cancer, 2021, 12(5): 1343 – 1355. doi: 10.7150/jca.50370
    [24] Liu JH, Jiang CH, Xu CJ, et al. Identification and development of a novel invasion - related gene signature for prognosis predic-tion in colon adenocarcinoma[J]. Cancer Cell International, 2021, 21(1): 101. doi: 10.1186/s12935-021-01795-1
    [25] Uddin N, Wang XS. Identification of key tumor stroma - associated transcriptional signatures correlated with survival prognosis and tumor progression in breast cancer[J]. Breast Cancer, 2022, 29(3): 541 – 561. doi: 10.1007/s12282-022-01332-6
    [26] Li Y, Wang YW, Chen X, et al. MicroRNA - 4472 promotes tumor proliferation and aggressiveness in breast cancer by targeting RGMA and inducing EMT[J]. Clinical Breast Cancer, 2020, 20(2): e113 – e126. doi: 10.1016/j.clbc.2019.08.010
    [27] Lu YJ, Li YR, Wang ZS, et al. Downregulation of RGMA by HIF - 1A/miR - 210 - 3p axis promotes cell proliferation in oral squa-mous cell carcinoma[J]. Biomedicine and Pharmacotherapy, 2019, 112: 108608. doi: 10.1016/j.biopha.2019.108608
    [28] Siebold C, Yamashita T, Monnier PP, et al. RGMs: structural in-sights, molecular regulation, and downstream signaling[J]. Trends in Cell Biology, 2017, 27(5): 365 – 378. doi: 10.1016/j.tcb.2016.11.009
    [29] Zhao ZW, Lian WJ, Chen GQ, et al. Decreased expression of repulsive guidance molecule member A by DNA methylation in colorectal cancer is related to tumor progression[J]. Oncology Reports, 2012, 27(5): 1653 – 1659.
    [30] Li Y, Liu HT, Chen X, et al. Aberrant promoter hypermethylation inhibits RGMA expression and contributes to tumor progression in breast cancer[J]. Oncogene, 2022, 41(3): 361 – 371. doi: 10.1038/s41388-021-02083-y
    [31] Schulten HJ, Hussein D. Array expression meta - analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas[J]. PLoS One, 2019, 14(5): e0215452. doi: 10.1371/journal.pone.0215452
    [32] Sepulveda JL, Gutierrez-Pajares JL, Luna A, et al. High - definition CpG methylation of novel genes in gastric carcinogenesis identified by next - generation sequencing[J]. Modern Pathology, 2016, 29(2): 182 – 193. doi: 10.1038/modpathol.2015.144
    [33] Wei L, Sun JJ, Zhang NS, et al. Noncoding RNAs in gastric cancer: implications for drug resistance[J]. Molecular Cancer, 2020, 19(1): 62. doi: 10.1186/s12943-020-01185-7
    [34] Zhang L, Kang WQ, Lu XL, et al. LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion in vitro by regulating cell cycle pathway[J]. Cell Cycle, 2018, 17(15): 1886 – 1900. doi: 10.1080/15384101.2018.1502574
    [35] Zhang J, Guo S, Piao HY, et al. ALKBH5 promotes invasion and metastasis of gastric cancer by decreasing methylation of the lncRNA NEAT1[J]. Journal of Physiology and Biochemistry, 2019, 75(3): 379 – 389. doi: 10.1007/s13105-019-00690-8
    [36] Chen HF, Ma RR, He JY, et al. Protocadherin 7 inhibits cell migration and invasion through E-cadherin in gastric cancer[J]. Tumour Biology, 2017, 39(4): 1010428317697551.
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  • 接收日期:  2022-04-04
  • 网络出版日期:  2022-12-26
  • 刊出日期:  2023-02-10

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