MAML1与胃癌进展和预后相关性的生物信息学分析

doi:10.3969/j.issn.1000-8535.2023.01.011

广州医药 ›› 2023, Vol. 54 ›› Issue (1): 56-63.DOI: 10.3969/j.issn.1000-8535.2023.01.011

MAML1与胃癌进展和预后相关性的生物信息学分析

陈梅¹, 张昱², 李冬梅¹, 张文静^1,3

1 昆明理工大学医学院(昆明 650500)
2 云南省第一人民医院,昆明理工大学附属医院消化内科(昆明 650032)
3 云南省第一人民医院,昆明理工大学附属医院肿瘤内科(昆明 650032)

收稿日期:2021-12-21 出版日期:2023-01-20 发布日期:2023-02-07
通讯作者: 张文静,E-mail:wenjing_zhang1@163.com
基金资助:
云南省万人计划青年拔尖人才项目(YNWR-QNBJ-2019-147);云南省医学学科带头人培养计划(D-2017002);云南省中青年学术和技术带头人后备人才(2018HB049)

Association between MAML1 and progression, prognosis in gastric cancer based on bioinformatics analysis

CHEN Mei¹, ZHAGN Yu², LI Dongmei¹, ZHANG Wenjing^1,3

1 Medical College of Kunming University of Science and Technology, Kunming 650500, China
2 Department of Digestive Medicine,the First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China
3 Department of Oncology, the First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China

Received:2021-12-21 Online:2023-01-20 Published:2023-02-07

摘要/Abstract

摘要： 目的通过多种生物信息学方法分析MAML1在GC患者中的表达及与临床特征、预后和免疫治疗疗效的相关性。方法利用TCGA数据库分析胃癌组织与正常胃黏膜组织中的MAML1表达水平;Kaplan-Meier在线工具对胃癌数据集GSE15459进行分析,阐明MAML1与患者临床特征及分期、治疗疗效的相关性;STRING软件预测与MAML1表达相关的基因,并用FUNRICH软件评估其富集的分子生物学功能和信号通路;TIMER和GEPIA数据库探索MAML1表达水平与肿瘤浸润免疫细胞及其相应基因标记集之间的关系。结果 MAML1在GC组织中的表达水平高于正常组织(P<0.001),且其表达水平与III期、有淋巴结转移、无远处转移的患者生存期相关(P<0.05),而与I、II和IV期、无淋巴结转移和有远处转移的患者生存期无相关性(P>0.05)。MAML1的相关作用基因主要分布在细胞核、参与转录调控,并且主要富集在雄激素受体、C-MYB转录因子和HIF-2α转录调控等相关的信号通路。MAML1表达水平与B细胞、CD4⁺ T细胞、巨噬细胞的表达水平存在正相关关系(P<0.05),但与肿瘤纯度、CD8⁺ T细胞、中性粒细胞、树突状细胞无相关性(P>0.05)。结论 MAML1有可能成为GC患者较差的临床预后标志物之一,其潜在分子机制可能与转录调控调节肿瘤微环境有关。

关键词: MAML1, 胃癌, 预后, 信号通路, 免疫治疗

Abstract: Objective To investigate the expression of MAML1 and its relationship with clinical characteristics, prognosis and the efficiency of immunotherapy in patients with GC. Methods MAML1 expression profile was observed by TCGA database. Kaplan-Meier survival analysis was applied to evaluate the correlation between the expression of MAML1 and clinical characteristics, prognosis and treatment efficiency of patients in GSE15459 dataset. MAML1-associated genes were predicted by STRING and were enriched in GO and KEGG by FUNRICH software. The relationship between MAML1 expression and markers of tumor infiltrated cells were explored by TIMER and GEPIA database. Results MAML1 was abnormally upregulated in GC tissues compared to normal gastric tissues (P<0.001). MAML1 expression was significantly associated with the overall survival of patients in stage III, with lymph node metastasis and without distant metastasis (P<0.001). There was no significant difference between MAML1 expression and the overall survival of patients in stage I, II, IV, without lymph node metastasis and with distant metastasis (P>0.05). MAML1-assoicated genes were mainly located at the nucleus, mediating transcriptional regulation and mainly enriching in androgen receptor, C-MYB transcription factor and HIF-2α transcription regulation and other related signaling pathways. MAML1 expression was positively related with the expression of B cell, CD4⁺ T cell and macrophages (P<0.05), but without significant difference with tumor purity, CD8⁺ T cell, neutrophils and dendritic cells (P>0.05). Conclusions MAML1 could be used as a marker of clinical prognosis of patients with GC. The potential molecular mechanism might be associated with its function in transcriptional regulation and changes in tumor microenvironment.

Key words: MAML1, gastric cancer, prognosis, signaling pathway, immunotherapy

陈梅, 张昱, 李冬梅, 张文静. MAML1与胃癌进展和预后相关性的生物信息学分析[J]. 广州医药, 2023, 54(1): 56-63.

CHEN Mei, ZHAGN Yu, LI Dongmei, ZHANG Wenjing. Association between MAML1 and progression, prognosis in gastric cancer based on bioinformatics analysis[J]. Guangzhou Medical Journal, 2023, 54(1): 56-63.

参考文献

[1] GUO Y, ZHANG Y, GERHARD M, et al. Effect of helicobacter pylori on gastrointestinal microbiota: a population-based study in Linqu, a high-risk area of gastric cancer[J]. Gut,2020, 69(9):1598-1607.
[2] LEE Y C, CHIANG T H, CHOU C K, et al. Association between helicobacter pylori eradication and gastric cancer incidence: a systematic review and Meta-analysis[J]. Gastroenterology,2016, 150(5):1113-1124.
[3] BOKU N. HER2-positive gastric cancer[J]. Gastric Cancer, 2014, 17(1):1-12.
[4] JHAVERI K L, WANG X V, MAKKER V, et al. Ado-trastuzumab emtansine (T-DM1) in patients with HER2 amplified tumors excluding breast and gastric/gastro-esophageal junction (GEJ) adenocarcinomas: Results from the NCI-MATCH Trial (EAY131) Sub-protocol Q[J]. Ann Oncol, 2019, 30(11):1821-1830.
[5] MONDACA S, MARGOIS M, SANCHEZ-VEGA F, et al. Phase II study of trastuzumab with modified docetaxel, cisplatin, and 5 fluorouracil in metastatic HER2-positive gastric cancer[J]. Gastric Cancer,2019, 22(2):355-362.
[6] GU L, CHEN M, GUO D, et al. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis[J]. PLoS One,2017, 12(8): e0182692.
[7] MURO K, CHUNG H C, SHANKARAN V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial[J]. Lancet Oncol,2016, 17(6):717-726.
[8] WU L, ASTER J C, BLAKLOW S C, et al. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors[J]. Nat Genet,2000, 26(4):484-489.
[9] KITAGAWA M, OYAMA T, KAWASHIMA T, et al. A human protein with sequence similarity to Drosophila mastermind coordinates the nuclear form of NOTCH and a CSL protein to build a transcriptional activator complex on target promoters[J]. Mol Cell Biol, 2001, 21(13):4337-4346.
[10] WANG Z, JENSEN M A, ZENKLUSEN J C. A practical guide to The Cancer Genome Atlas (TCGA)[J]. Methods Mol Biol, 2016(1418):111-141.
[11] OOI C H, IVANOVA T, WU J, et al. Oncogenic pathway combinations predict clinical prognosis in gastric cancer[J]. PLoS Genet,2009, 5(10): e1000676.
[12] SZKLARCZYK D, GABLE A L, LYON D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Res,2019, 47(D1): D607-D613.
[13] PATHAN M, KEERTHIKUMAR S, ANG C S, et al. FunRich: An open access standalone functional enrichment and interaction network analysis tool[J]. Proteomics,2015, 15(15):2597-2601.
[14] 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.
[15] LI B, SEVERSON E, PIGNON J C, et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy[J]. Genome Biology, 2016, 17(1):174.
[16] HASHEMI BIDOKHTI M, ABBASZADEGAN M R, SHARIFI N, et al. Contribution of MAMLI in esophageal squamous cell carcinoma tumorigenesis[J]. Ann Diagn Pathol,2017(27):79-82.
[17] FORGHANIFARD M M, MOAVEN O, FARSHCHIAN M, et al. Expression analysis elucidates the roles of MAML1 and Twist1 in esophageal squamous cell carcinoma aggressiveness and metastasis[J]. Ann Surg Oncol,2012, 19(3):743-749.
[18] MOGHBELI M, MOSANNEN MOZAFFARI H, MEMAR B, et al. Role of MAML1 in targeted therapy against the esophageal cancer stem cells[J]. J Transl Med,2019, 17(1):126.
[19] HIBDON E S, RAZUMILAVA N, KEELEY T M, et al. NOTCH and mTOR signaling pathways promote human GC cell proliferation[J]. Neoplasia,2019, 21(7):702-712.
[20] LIU J, SATO C, CERLETTI M, et al. NOTCH signaling in the regulation of stem cell self-renewal and differentiation[J]. Curr Top Dev Biol, 2010(92):367-409.
[21] GENG Y, FAN J, CHEN L, et al. A NOTCH-dependent inflammatory feedback circuit between macrophages and cancer cells regulates pancreatic cancer metastasis[J]. Cancer Res, 2021, 81(1):64-76.
[22] BOUSQUET MUR E, BERNARDO S, PAPON L, et al. NOTCH inhibition overcomes resistance to tyrosine kinase inhibitors in EGFR-driven lung adenocarcinoma[J]. J Clin Invest,2020, 130(2):612-624.
[23] KIM W, KHAN S K, GVOZDENOVIC-JEREMIC J, et al. Hippo signaling interactions with Wnt/β-catenin and NOTCH signaling repress liver tumorigenesis[J]. J Clin Invest, 2017, 127(1):137-152.
[24] FERRANDINO F, GRAZIOLI P, BELLAVIA D, et al. NOTCH and NF-κB: Coach and players of regulatory t-cell response in cancer[J]. Front Immunol,2018(9):2165.
[25] ROEMER K. NOTCH and the p53 clan of transcription factors[J]. Adv Exp Med Biol,2012(727):223-240.
[26] PELISH H E, LIAU B B, NITULESCU I I, et al. Mediator kinase inhibition further activates super-enhancer-associated genes in AML[J]. Nature,2015, 526(7572):273-276.
[27] RZYMSKI T, MIKULA M, ZYLKIEWICZ E, et al. SEL120-34A is a novel CDK8 inhibitor active in AML cells with high levels of serine phosphorylation of STAT1 and STAT5 transactivation domains[J]. Oncotarget,2017, 8(20):33779-33795.
[28] KANG S, XIE J, MIAO J, et al. A knockdown of Maml1 that results in melanoma cell senescence promotes an innate and adaptive immune response[J]. Cancer Immunol Immunother, 2013, 62(1):183-190.

MAML1与胃癌进展和预后相关性的生物信息学分析

Association between MAML1 and progression, prognosis in gastric cancer based on bioinformatics analysis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	方子晗, 喻祖豪, 刘颖, 杨振, 王可. ABCC2基因过表达对肺腺癌预后的影响[J]. 广州医药, 2022, 53(6): 109-118.
[2]	王建, 彭芳, 王志, 孙雪骐. 胃肠道套细胞淋巴瘤的临床病理学特点分析及预后影响因素分析[J]. 广州医药, 2022, 53(6): 133-137.
[3]	张慧芳, 罗凤, 张丽君. 团体认知行为干预联合揿针全程护理对胃癌晚期癌痛患者心理状态的影响[J]. 广州医药, 2022, 53(4): 114-117.
[4]	陈婷女, 梁慕琼, 梁亮. 儿童重症肺炎支气管肺泡灌洗液病原学及疾病预后分析[J]. 广州医药, 2022, 53(3): 53-56.
[5]	刘颖, 方子晗, 张雅琴, 王可. DNA甲基化位点对肺腺癌预后的作用研究[J]. 广州医药, 2022, 53(3): 112-117.
[6]	王俊, 闫娅, 李永红, 李佳. 分析CT肺动脉栓塞指数与急性肺栓塞患者右心功能及预后的相关性[J]. 广州医药, 2022, 53(2): 120-123.
[7]	吴天源, 罗义, 吕磊, 谭文亮, 孙少喜. CYP2C19基因多态性与急性心肌梗死患者炎症指标、临床预后的相关性[J]. 广州医药, 2022, 53(1): 1-5.
[8]	陶豫东. 益生菌结合肠内营养干预纠正缺血性急性脑卒中患者肠道菌落紊乱的作用及对其预后的影响[J]. 广州医药, 2022, 53(1): 109-113.
[9]	肖驰, 周雪, 徐丹, 杨美英, 费晶, 巩平. SNCG在卵巢癌中的表达及其临床意义[J]. 广州医药, 2021, 52(5): 1-7.
[10]	古嘉基, 连泳欣, 丘福满. m6A甲基化基因风险评估模型在卵巢癌预后的临床意义[J]. 广州医药, 2021, 52(3): 1-8.
[11]	谢艳林, 董燕, 柳建华. 经胸超声心动图在Stanford A型主动脉夹层的诊断及预后评估中的价值[J]. 广州医药, 2021, 52(3): 36-40.
[12]	罗水妹, 黄颂平, 许白兰, 沈冰寒. 肺癌并发肺栓塞的危险因素及预后分析[J]. 广州医药, 2021, 52(2): 40-45.
[13]	钟雄东. 丹参有效成分——二氢丹参酮Ⅰ抑制胃癌的作用研究[J]. 广州医药, 2020, 51(6): 11-18.
[14]	黄子圣, 黄迪, 黄宇, 何志翔, 李佩霖, 翁杰锋, 李桃生, 古维立. 细胞间质液压升高对肝星状细胞的影响[J]. 广州医药, 2020, 51(5): 130-134.
[15]	岑昕贝, 凌济忠, 万跃平, 万颂, 华伟, 江敏耀, 习明. NR3C1表达与前列腺癌生化复发的相关性研究[J]. 广州医药, 2020, 51(4): 22-27.