title: Comprehensive transcriptome analysis identifies pathways with therapeutic potential in locally advanced cervical cancer.
abstract: OBJECTIVE
  The objective of the present study was to provide genomic and transcriptomic information that may improve clinical outcomes for locally advanced cervical cancer (LACC) patients by searching for therapeutic targets or potential biomarkers through the analysis of significantly altered signaling pathways in LACC.
  
  
  METHODS
  Microarray-based transcriptome profiling of 89 tumor samples from women with LACC was performed. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, significantly over-expressed genes in LACC were identified; these genes were validated by quantitative reverse transcription-polymerase chain reaction in an independent cohort, and the protein expression data were obtained from the Human Protein Atlas.
  
  
  RESULTS
  A transcriptome analysis revealed 7530 significantly over-expressed genes in LACC samples. By KEGG analysis, we found 93 dysregulated signaling pathways, including the JAK-STAT, NOTCH and mTOR-autophagy pathways, which were significantly upregulated. We confirmed the overexpression of the relevant genes of each pathway, such as NOTCH1, JAK2, STAM1, SOS1, ADAM17, PSEN1, NCSTN, RPS6, STK11/LKB1 and MLTS8/GBL in LACC compared with normal cervical tissue epithelia.
  
  
  CONCLUSIONS
  Through comprehensive genomic and transcriptomic analyses, this work provides information regarding signaling pathways with promising therapeutic targets, suggesting novel target therapies to be considered in future clinical trials for LACC patients.
authors: Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico.
authors: Alma Delia
authors: AD
authors: Campos-Parra
authors: Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico.
authors: Alejandra
authors: A
authors: Padua-Bracho
authors: Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico.
authors: Abraham
authors: A
authors: Pedroza-Torres
authors: Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico.
authors: Gabriela
authors: G
authors: Figueroa-González
authors: Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico.
authors: Jorge
authors: J
authors: Fernández-Retana
authors: Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico.
authors: Oliver
authors: O
authors: Millan-Catalan
authors: Dirección de Infecciones Crónicas y Cáncer, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico.
authors: Oscar
authors: O
authors: Peralta-Zaragoza
authors: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico.
authors: David
authors: D
authors: Cantú de León
authors: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico.
authors: Luis A
authors: LA
authors: Herrera
authors: Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Col. Sección XVI, C.P. 14080 Tlalpan, Ciudad de Mexico, Mexico; Unidad de Biomedicina, FES-IZTACALA, Universidad Nacional Autónoma de México (UNAM), Avenida De Los Barrios S/N, Los Reyes Iztacala, C.P. 54090 Tlanepantla, Ciudad de Mexico, Mexico. Electronic address: carlos.pplas@gmail.com.
authors: Carlos
authors: C
authors: Pérez-Plasencia
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D059467:Transcriptome; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
chemical_list: D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
keywords: Genomic and transcriptome analysis; Locally advanced cervical cancer; Therapeutic targets