Bioinformatics analyses of the differences between lung adenocarcinoma and squamous cell carcinoma using The Cancer Genome Atlas expression data

The present study aimed to explore gene and microRNA (miRNA) expression differences between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified by analyzing mRNA and miRNA expression data in normal and cancerous lung tissues that were obtained from The Cancer Genome Atlas database. A total of 778 DEGs and 7 DEMs were identified. Altered gene functions and signaling pathways were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, which revealed that DEGs were significantly enriched in extracellular matrix organization, cell differentiation, negative regulation of toll signaling pathway, and several other terms and pathways. Transcription factor (TF)-miRNA-gene networks in LUAD and LUSC were predicted using the TargetScan, Miranda, and TRANSFAC databases, which revealed the regulatory links among the TFs, DEMs, and DEGs. The central TFs, i.e., the TFs in the middle of the TF-miRNA-gene network, of LUAD and LUSC were similar. Although LUAD and LUSC shared similar miRNAs in the predicted networks, miR-29b-3p was demonstrated to be upregulated only in LUAD, whereas miR-1, miR-105-5p, and miR-193b-5p were altered in LUSC. These findings may improve our understanding of the different molecular mechanisms in non-small cell lung cancers and may promote new and accurate strategies for prevention, diagnosis, and treatment.

[1]  H. Hansen,et al.  Lung cancer. , 1990, Cancer chemotherapy and biological response modifiers.

[2]  K. Mimori,et al.  miR-29b is an indicator of prognosis in breast cancer patients. , 2015, Molecular and clinical oncology.

[3]  D. Bartel,et al.  Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs , 2011, Nature Structural &Molecular Biology.

[4]  J. Roman,et al.  Peroxisome proliferator-activated receptor &ggr;: a novel target for cancer therapeutics? , 2007, Anti-cancer drugs.

[5]  N. Seki,et al.  microRNA-1/133a and microRNA-206/133b clusters: Dysregulation and functional roles in human cancers , 2012, Oncotarget.

[6]  S. Lippman,et al.  Lung cancer. , 2008, The New England journal of medicine.

[7]  L. Byers,et al.  Smoking , p 53 Mutation , and Lung Cancer , 2014 .

[8]  Wei Zhang,et al.  Relative expressions of miR-205-5p, miR-205-3p, and miR-21 in tissues and serum of non-small cell lung cancer patients , 2013, Molecular and Cellular Biochemistry.

[9]  P. Eastman.  Annual Report on Status of Cancer from ACS, NCI, CDC, Cancer Registries: Targeted Focus on Latinos Will Likely Improve US Cancer Rates , 2006 .

[10]  A. Schwartz,et al.  Diagnostic surgical pathology in lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. , 2013, Chest.

[11]  C. Zhan,et al.  Expression profile analysis of head and neck squamous cell carcinomas using data from The Cancer Genome Atlas , 2016, Molecular medicine reports.

[12]  W. Travis,et al.  Pathological diagnosis and classification of lung cancer in small biopsies and cytology: strategic management of tissue for molecular testing. , 2011, Seminars in respiratory and critical care medicine.

[13]  Susumu Goto,et al.  The KEGG resource for deciphering the genome , 2004, Nucleic Acids Res..

[14]  T. Jacks,et al.  The differential effects of mutant p53 alleles on advanced murine lung cancer. , 2005, Cancer research.

[15]  Anjali J. Koppal,et al.  Supplementary data: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites , 2010 .

[16]  Y. Yatabe,et al.  Molecular and Cellular Pathobiology Mir-375 Is Activated by Ash1 and Inhibits Yap1 in a Lineage-dependent Manner in Lung Cancer , 2022 .

[17]  Jianhong Zhou,et al.  Mir-375 enhances ruthenium-derived compound Rawq01 induced cell death in human ovarian cancer. , 2013, International journal of clinical and experimental pathology.

[18]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[19]  D. Radisky,et al.  Tumor cell expression of MMP3 as a prognostic factor for poor survival in pancreatic, pulmonary, and mammary carcinoma , 2015, Genes & cancer.

[20]  D. Radisky,et al.  Matrix Metalloproteinase-Induced Epithelial-Mesenchymal Transition in Breast Cancer , 2010, Journal of Mammary Gland Biology and Neoplasia.

[21]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[22]  Richard Simon,et al.  A random variance model for detection of differential gene expression in small microarray experiments , 2003, Bioinform..

[23]  Helena Carreira,et al.  Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2) , 2015, The Lancet.

[24]  Lawrence A. Donehower,et al.  A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53–deficient mice , 1995, Nature Genetics.

[25]  Z. Werb,et al.  Matrix Metalloproteinases: Regulators of the Tumor Microenvironment , 2010, Cell.

[26]  L. Donehower,et al.  Reduction of p53 gene dosage does not increase initiation or promotion but enhances malignant progression of chemically induced skin tumors , 1993, Cell.

[27]  K. Ghoshal,et al.  Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. , 2018, The Journal of Biological Chemistry.

[28]  Alexander E. Kel,et al.  MATCHTM: a tool for searching transcription factor binding sites in DNA sequences , 2003, Nucleic Acids Res..

[29]  M. Kondo,et al.  Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptor-gamma agonists through induction of apoptosis. , 2000, Biochemical and biophysical research communications.

[30]  Jie He,et al.  Annual report on status of cancer in China, 2011. , 2015, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[31]  Lin Jiang,et al.  Decreased circulating miR-375: A potential biomarker for patients with non-small-cell lung cancer. , 2014, Gene.

[32]  M. Ladanyi,et al.  Clarifying the Spectrum of Driver Oncogene Mutations in Biomarker-Verified Squamous Carcinoma of Lung: Lack of EGFR/KRAS and Presence of PIK3CA/AKT1 Mutations , 2012, Clinical Cancer Research.

[33]  E. Wingender,et al.  MATCH: A tool for searching transcription factor binding sites in DNA sequences. , 2003, Nucleic acids research.

[34]  Masahiro Tsuboi,et al.  International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[35]  J. Baak,et al.  Validation of Expression Patterns for Nine miRNAs in 204 Lymph-Node Negative Breast Cancers , 2012, PloS one.

[36]  Feng Jiang,et al.  Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer , 2015, Laboratory Investigation.

[37]  N. Seki,et al.  Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C , 2014, Journal of Human Genetics.

[38]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[39]  K. Mimori,et al.  miR ‐ 29 b is an indicator of prognosis in breast cancer patients , 2015 .

[40]  C. Zhan,et al.  Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma. , 2015, Journal of thoracic disease.

[41]  L. Yan,et al.  Landscape of expression profiles in esophageal carcinoma by The Cancer Genome Atlas data. , 2016, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[42]  Feng Jiang,et al.  Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers , 2010, International journal of cancer.

[43]  L. Byers,et al.  Smoking, p53 Mutation, and Lung Cancer , 2014, Molecular Cancer Research.

[44]  Steven J. M. Jones,et al.  Comprehensive genomic characterization of squamous cell lung cancers , 2012, Nature.

[45]  V. Rusch,et al.  Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift. , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.