论著 · 基础研究

MRPL12在肺腺癌中的表达和预后分析

  • 熊雷 ,
  • 易茜 ,
  • 许明芳 ,
  • 陈健
展开
  • 1.重庆市渝北区人民医院门诊手术室,重庆 401120
    2.重庆佑佑宝贝妇儿医院儿内科,重庆 401120
    3.陆军特色医疗中心肿瘤科,重庆 400042
熊 雷(1989—),男,主治医师,硕士;电子信箱:1044232072@qq.com
陈 健,电子信箱:18021706@qq.com

网络出版日期: 2021-08-13

基金资助

重庆自然科学基金(cstc2020jcyj-msxmX0233)

Expression and prognosis analysis of MRPL12 in lung adenocarcinoma

  • Lei XIONG ,
  • Qian YI ,
  • Ming-fang XU ,
  • Jian CHEN
Expand
  • 1.Outpatient Service Operating Room, Chongqing Yubei District People's Hospital, Chongqing 401120, China
    2.Department of Paediatric Internal Medicine, Chongqing Youyou Baby Women's and Children's Hospital, Chongqing 401120, China
    3.Department of Oncology, Featured Medical Center of The Chinese People's Liberation Army, Chongqing 400042, China
CHEN Jian, E-mail: 18021706@qq.com.

Online published: 2021-08-13

Supported by

Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0233)

摘要

目的·分析线粒体核糖体蛋白L12(mitochondrial ribosomal protein L12,MRPL12)在肺腺癌(lung adenocarcinoma,LUAD)和正常组织中的表达差异和对患者预后的影响,以及预测其生物学功能。方法·利用肿瘤浸润性免疫细胞分析数据库TIMER和GEPIA(gene expression profiling and interactive analyses)交互式网站服务器分析癌症基因组图谱(The Cancer Genome Atlas,TCGA)中MRPL12在不同癌组织中的表达情况的影响。利用Sangerbox生物信息分析平台对MRPL12差异表达的癌症类型进行Cox回归和Kaplan-Meier生存分析,评估风险比(hazard ratio,HR)、95%置信区间(confidence interval,CI)和Log-rank P值。采用UALCAN数据分析平台评估MRPL12蛋白表达与临床病理参数的关系。使用LinkedOmics数据库筛选与MRPL12表达相关的基因。采用DAVID数据库进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。定量聚合酶链反应验证MRPL12在细胞中的转录水平。结果·MRPL12在多种癌组织中显著高表达,但只有在LUAD中MRPL12的高表达与患者较差的总体生存期(overall suivival,OS)和疾病特异性生存期(disease-specific survival,DSS)相关;肿瘤分级程度越高的LUAD患者MRPL12蛋白表达水平越高;在LUAD基因表达数据集中与MRPL12负相关的基因富集到癌症通路(P=0.000)、癌症蛋白聚糖(P=0.000)、非小细胞肺癌(P=0.000)等癌症相关的通路。MRPL12在LUAD细胞(H1395、H1975和HCC827)中的mRNA表达水平高于正常细胞(Beas-2B),差异有统计学意义(P<0.05)。结论·MRPL12高表达的LUAD患者可能预后较差;MRPL12可以作为LUAD预后不良的潜在生物标志物和潜在的治疗新靶点。

本文引用格式

熊雷 , 易茜 , 许明芳 , 陈健 . MRPL12在肺腺癌中的表达和预后分析[J]. 上海交通大学学报(医学版), 2021 , 41(8) : 1033 -1040 . DOI: 10.3969/j.issn.1674-8115.2021.08.006

Abstract

Objective

·To analyze the difference of expression of mitochondrial ribosomal protein L12 (MRPL12) in lung adenocarcinoma (LUAD) and normal tissues and its influence on the prognosis of patients, and predict its biological function.

Methods

·The expressions of MRPL12 in different cancer tissues were analyzed by The Cancer Genome Atlas (TCGA) using the tumor-infiltrating immune cell analysis database TIMER and GEPIA (gene expression profiling and interactive analyses) server. The expressions of MRPL12 in different types of cancer were analyzed by Sangerbox bioinformatics platform. Cox regression and Kaplan-Meier survival analysis were used and the hazard ratios (HR), the 95% confidence intervals (CI) and the Log-rank P values were evaluated. The LinkedOmics database was used to identify the genes associated with MRPL12 expression. The DAVID database was used for the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The transcription levels of MRPL12 in cells were verified by quantitative PCR (qPCR).

Results

·MRPL12 was highly expressed in many cancer types. But only the LUAD patients with high MRPL12 expression had lower overall survival (OS) and disease-specific survival (DSS). The expression of MRPL12 protein increased with tumor stage and individual tumor grade. The genes negatively related to MRPL12 were enriched into several cancer-related pathways in LUAD gene expression data set, including pathways in cancer (P=0.000), proteoglycans in cancer (P=0.000) and non-small cell lung cancer (P=0.000). The mRNA expression levels of MRPL12 in the LUAD cells (H1395, H1975 and HCC827) were higher than that in the normal cell (Beas-2B), and the difference was statistically significant (P<0.05).

Conclusion

·The LUAD patients with high expression of MRPL12 may have poor prognosis, and thus MRPL12 can be a potential biomarker and potential therapeutic target for LUAD.

参考文献

1 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.
2 Wu C, Li M, Meng H, et al. Analysis of status and countermeasures of cancer incidence and mortality in China[J]. Sci China Life Sci, 2019, 62(5): 640-647.
3 Villalobos P, Wistuba II. Lung cancer biomarkers[J]. Hematol Oncol Clin North Am, 2017, 31(1): 13-29.
4 Lennon FE, Salgia R. Mitochondrial dynamics: biology and therapy in lung cancer[J]. Expert Opin Investig Drugs, 2014, 23(5): 675-692.
5 Porporato PE, Filigheddu N, Pedro JMB, et al. Mitochondrial metabolism and cancer[J]. Cell Res, 2018, 28(3): 265-280.
6 Kim HJ, Maiti P, Barrientos A. Mitochondrial ribosomes in cancer[J]. Semin Cancer Biol, 2017, 47: 67-81.
7 Senft D, Ronai ZA. Regulators of mitochondrial dynamics in cancer[J]. Curr Opin Cell Biol, 2016, 39: 43-52.
8 Marty L, Taviaux S, Fort P. Expression and human chromosomal localization to 17q25 of the growth-regulated gene encoding the mitochondrial ribosomal protein MRPL12[J]. Genomics, 1997, 41(3): 453-457.
9 Wang ZB, Cotney J, Shadel GS. Human mitochondrial ribosomal protein MRPL12 interacts directly with mitochondrial RNA polymerase to modulate mitochondrial gene expression[J]. J Biol Chem, 2007, 282(17): 12610-12618.
10 Serre V, Rozanska A, Beinat M, et al. Mutations in mitochondrial ribosomal protein MRPL12 leads to growth retardation, neurological deterioration and mitochondrial translation deficiency[J]. Biochim Biophys Acta, 2013, 1832(8): 1304-1312.
11 Sy SM, Wong N, Mok TS, et al. Genetic alterations of lung adenocarcinoma in relation to smoking and ethnicity[J]. Lung Cancer, 2003, 41(1): 91-99.
12 Li T, Fu J, Zeng Z, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells[J]. Nucleic Acids Res, 2020, 48(w1): W509-W514.
13 Tang ZF, Li CW, Kang BX, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res, 2017, 45(W1): W98-W102.
14 Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses[J]. Neoplasia, 2017, 19(8): 649-658.
15 Vasaikar SV, Straub P, Wang J, et al. LinkedOmics: analyzing multi-omics data within and across 32 cancer types[J]. Nucleic Acids Res, 2018, 46(d1): D956-D963.
16 Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J]. Nat Protoc, 2009, 4(1): 44-57.
17 Pao W, Girard N. New driver mutations in non-small-cell lung cancer[J]. Lancet Oncol, 2011, 12(2): 175-180.
18 Cagle PT, Allen TC, Olsen RJ. Lung cancer biomarkers: present status and future developments[J]. Arch Pathol Lab Med, 2013, 137(9): 1191-1198.
19 邓垒, 张文珏, 周宗玫, 等. 327例广泛期小细胞肺癌综合治疗的疗效分析[J]. 国际放射医学核医学杂志, 2018, 42(1): 1-8.
20 Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer[J]. N Engl J Med, 2018, 378(2): 113-125.
21 Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study[J]. Lancet, 2017, 389(10072): 917-929.
22 Surovtseva YV, Shutt TE, Cotney J, et al. Mitochondrial ribosomal protein L12 selectively associates with human mitochondrial RNA polymerase to activate transcription[J]. PNAS, 2011, 108(44): 17921-17926.
23 Amunts A, Brown A, Toots J, et al. Ribosome. The structure of the human mitochondrial ribosome[J]. Science, 2015, 348(6230): 95-98.
24 Lamb R, Ozsvari B, Lisanti CL, et al. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease[J]. Oncotarget, 2015, 6(7): 4569-4584.
25 Marty L, Fort P. A delayed-early response nuclear gene encoding MRPL12, the mitochondrial homologue to the bacterial translational regulator L7/L12 protein[J]. J Biol Chem, 1996, 271(19): 11468-11476.
26 Nouws J, Goswami AV, Bestwick M, et al. Mitochondrial ribosomal protein L12 is required for POLRMT stability and exists as two forms generated by alternative proteolysis during import[J]. J Biol Chem, 2016, 291(2): 989-997.
27 Zhang QL, Liang Z, Gao YX, et al. Differentially expressed mitochondrial genes in breast cancer cells: potential new targets for anti-cancer therapies[J]. Gene, 2017, 596: 45-52.
28 Vatapalli R, Sagar V, Rodriguez Y, et al. Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer[J]. Nat Commun, 2020, 11(1): 4153.
29 Ge Z, Guo X, Li JY, et al. Clinical significance of high c-MYC and low MYCBP2 expression and their association with Ikaros dysfunction in adult acute lymphoblastic leukemia[J]. Oncotarget, 2015, 6(39): 42300-42311.
30 Müller J, Eilers M. Ubiquitination of Myc: proteasomal degradation and beyond[J]. Ernst Schering Found Symp Proc, 2008(1): 99-113.
文章导航

/