基于生物信息学分析挖掘非小细胞肺癌中的预后基因
Mining Prognostic Genes in Non-Small Cell Lung Cancer Based on Bioinformatics Analysis
摘要: 非小细胞肺癌(non-small cell lung cancer, NSCLC)仍是当今世界死亡率最高的恶性肿瘤,但其发生和发展的分子机制的改变仍不清楚。本研究中,我们通过基因表达综合(Gene Expression Omnibus, GEO)数据库下载基因表达微阵列数据GSE11830,例用edgeR软件筛选肿瘤组织及周围正常组织之间上调和下调最明显的20个差异基因。为进一步了解差异基因的功能及机制,我们通过基因本体论(Gene Ontology, GO)数据库及京都基因与基因组百科全书(Kyoto Encyclopedia of Gene and Genomes, KEGG)数据库对这40个差异基因的进行功能及通路富集进行分析。此外,我们通过癌症基因组数据库(The Cancer Genome Atlas, TCGA)下载NSCLC患者的临床信息,并对40个差异基因进行生存分析,发现5个上调基因及3个下调基因与NSCLC生存期影响较为显著。利用cBioPortal可视化工具对这8个关键基因进行基因突变及DNA扩增频率的分析,发现PKHD1L1、MME和IGSF10可能是NSCLC发生及影响预后的关键基因。
Abstract: Non-small cell lung cancer (NSCLC) is still the malignant tumor with the highest mortality rate in the world, but the molecular mechanism of occurrence and development of NSCLC is still unclear. In this study, we downloaded gene expression microarray data GSE11830 through the Gene Expression Omnibus (GEO) database, and used the edgeR software to screen the 20 most significantly up-regulated and down-regulated genes between tumor tissues and surrounding normal tissues. In order to further understand the functions and mechanisms of differential genes, we used the Gene Ontology (GO) database and the Kyoto Encyclopedia of Gene and Genomes (KEGG) database to perform enrichment analysis of these 40 differential genes. In addition, we downloaded the clinical information of NSCLC patients through The Cancer Genome Atlas (TCGA), and analyzed the survival of 40 differential genes, and found that 5 up-regulated genes and 3 down-regulated genes have a significant impact on NSCLC survival. In addition, we use cBioPortal which was a visualization tool to analyze the gene mutation and DNA amplification frequency of these 8 key genes, and it is found that PKHD1L1, MME and IGSF10 may be the key genes for the occurrence and prognosis of NSCLC.
文章引用:韩骐蔓, 朱静娟, 张传涛, 王力, 张晓春. 基于生物信息学分析挖掘非小细胞肺癌中的预后基因[J]. 临床医学进展, 2021, 11(4): 1655-1664. https://doi.org/10.12677/ACM.2021.114238

参考文献

[1] Zarogoulidis, K., Zarogoulidis, P., Darwiche, K., Boutsikou, E. and Machairiotis, N. (2013) Treatment of Non-Small Cell Lung Cancer (NSCLC). Journal of Thoracic Disease, 5, S389-S396.
[2] Mitsudomi, T., Morita, S., Yatabe, Y., Negoro, S., Okamoto, I., Tsurutani, J., et al. (2010) Gefitinib versus Cisplatin plus Docetaxel in Patients with Non-Small-Cell Lung Cancer Harbouring Mutations of the Epidermal Growth Factor Receptor (WJTOG3405): An Open Label, Randomised Phase 3 Trial. The Lancet Oncology, 11, 121-128. [Google Scholar] [CrossRef
[3] Hirsch, F.R. and Bunn, P.A. (2009) EGFR Testing in Lung Cancer Is Ready for Prime Time. The Lancet Oncology, 10, 432-433. [Google Scholar] [CrossRef
[4] Soda, M., Choi, Y.L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., et al. (2007) Identification of the Transforming EML4-ALK Fusion Gene in Non-Small-Cell Lung Cancer. Nature, 448, 561-566. [Google Scholar] [CrossRef] [PubMed]
[5] Miller, K.D., Nogueira, L., Mariotto, A.B., Rowland, J.H. and Siegel, R.L. (2019) Cancer Treatment and Survivorship Statistics, 2019. CA: A Cancer Journal for Clinicians, 69, 363-385. [Google Scholar] [CrossRef] [PubMed]
[6] Ding, Y., Yang, D.Z., Zhai, Y.N., Xue, K. and Wang, S.M. (2017) Microarray Expression Profiling of Long Non-Coding RNAs in Epithelial Ovarian Cancer. Oncology Letters, 14, 2523-2530. [Google Scholar] [CrossRef] [PubMed]
[7] Smyth, G.K. (2005) Limma: Linear Models for Microarray Data. In: Bioinformatics and Computational Biology Solutions Using R and Bioconductor, Springer, New York, 397-420. [Google Scholar] [CrossRef
[8] Sun, X. Li, J. (2013) Pairheatmap: Comparing Expression Profiles of Gene Groups in Heatmaps. Computer Methods and Programs in Biomedicine, 112, 599-606. [Google Scholar] [CrossRef] [PubMed]
[9] Mccarthy, D.J., Yunshun, C. and Smyth, G.K. (2012) Differential Expression Analysis of Multifactor RNA-Seq Experiments with Respect to Biological Variation. Nucleic Acids Research, 40, 4288-4297. [Google Scholar] [CrossRef] [PubMed]
[10] Fox, J. and Carvalho, M.S. (2012) The RcmdrPlugin.survival Package: Extending the R Commander Interface to Survival Analysis. Journal of Statistical Software, 49, 1-32. [Google Scholar] [CrossRef
[11] Tang, Z., et al. (2017) GEPIA: A Web Server for Cancer and Normal Gene Expression Profiling and Interactive Analyses. Nucleic Acids Research, 45, W98-W102. [Google Scholar] [CrossRef] [PubMed]
[12] Lian, P.W., Fu, Y.L., Li, A., Dai, B.Z. and Wu, G.Q. (2011) Preparation and Characterization of a Polyclonal Antibody against Human Fibrocystin-L. Chinese Journal of Cellular & Molecular Immunology, 27, 78-81.
[13] Hogan, M.C., Griffin, M.D., Sandro, R., Torres, V.E., Ward, C.J. and Harris, P.C. (2003) PKHDL1, a Homolog of the Autosomal Recessive Polycystic Kidney Disease Gene, Encodes a Receptor with Inducible T Lymphocyte Expression. Human Molecular Genetics, 12, 685-698. [Google Scholar] [CrossRef] [PubMed]
[14] Zheng, C., Quan, R., Xia, E.J., Bhandari, A. and Zhang, X. (2019) Original Tumour Suppressor Gene Polycystic Kidney and Hepatic Disease 1-Like 1 Is Associated with Thyroid Cancer Cell Progression. Oncology Letters, 18, 3227-3235. [Google Scholar] [CrossRef] [PubMed]
[15] Makrogkikas, S. (2017) Molecular and Cellular Mechanism of Function of the PKHD1L1 Gene in Vertebrates. Mechanisms of Development, 145, S64. [Google Scholar] [CrossRef
[16] Suzuki, A., Fukushige, S., et al. (1997) Frequent Gains on Chromosome Arms 1q and/or 8q in Human Endometrial Cancer. Human Genetics, 100, 629-636. [Google Scholar] [CrossRef] [PubMed]
[17] Iżykowska, K., et al. (2014) Submicroscopic Genomic Rearrangements Change Gene Expression in T-Cell Large Granular Lymphocyte Leukemia. European Journal of Haematology, 93, 143-149. [Google Scholar] [CrossRef] [PubMed]
[18] Pascale, G., Livstone, M.S., Lewis, S.E. and Thomas, P.D. (2011) Phylogenetic-Based Propagation of Functional Annotations within the Gene Ontology Consortium. Briefings in Bioinformatics, 12, 449-462. [Google Scholar] [CrossRef] [PubMed]
[19] Skidgel, R.A., et al. (1984) Hydrolysis of Substance P and Neurotensin by Converting Enzyme and Neutral Endopeptidase. Peptides, 5, 769-776. [Google Scholar] [CrossRef] [PubMed]
[20] Spencer, B., Verma, I., Desplats, P., Morvinski, D., Rockenstein, E., Adame, A., et al. (2014) A Neuroprotective Brain-Penetrating Endopeptidase Fusion Protein Ameliorates Alzheimer Disease Pathology and Restores Neurogenesis. Journal of Biological Chemistry, 289, 17917-17931. [Google Scholar] [CrossRef
[21] Thomas, B.C., Kay, J.D., Menon, S., Vowler, S.L., Dawson, S.N., Bucklow, L.J., et al. (2016) Whole Blood mRNA in Prostate Cancer Reveals a Four-Gene Androgen Regulated Panel. Endocrine Related Cancer, 23, 797-812. [Google Scholar] [CrossRef
[22] Sumitomo, M., Iwase, A., Zheng, R., Navarro, D. and Nanus, D.M. (2004) Synergy in Tumor Suppression by Direct Interaction of Neutral Endopeptidase with PTEN. Cancer Cell, 5, 67-78. [Google Scholar] [CrossRef
[23] Osman, I. (2004) Neutral Endopeptidase Protein Expression and Prognosis in Localized Prostate Cancer. Clinical Cancer Research, 10, 4096-4100. [Google Scholar] [CrossRef
[24] Daino, K., Ugolin, N., Altmeyer-Morel, S., Guilly, M.-N. and Chevillard, S. (2009) Gene Expression Profiling of Alpha-Radiation-Induced Rat Osteosarcomas: Identification of Dysregulated Genes Involved in Radiation-Induced Tumorigenesis of Bone. International Journal of Cancer, 125, 612-620. [Google Scholar] [CrossRef] [PubMed]
[25] Ling, B., Liao, X., Huang, Y., Liang, L., Jiang, Y., Pang, Y., et al. (2020) Identification of Prognostic Markers of Lung Cancer through Bioinformatics Analysis and in Vitro Experiments. International Journal of Oncology, 56, 193-205.
[26] Wu, M., Li, Q. and Wang, H. (2021) Identification of Novel Biomarkers Associated with the Prognosis and Potential Pathogenesis of Breast Cancer via Integrated Bioinformatics Analysis. Technology in Cancer Research & Treatment, 20, 1533033821992081. [Google Scholar] [CrossRef] [PubMed]
[27] Thutkawkorapin, J., Picelli, S., Kontham, V., Liu, T., Nilsson, D. and Lindblom, A. (2016) Exome Sequencing in One Family with Gastric- and Rectal Cancer. BMC Genetics, 17, 41. [Google Scholar] [CrossRef] [PubMed]