title: A microRNA expression signature for clinical response in locally advanced cervical cancer.
abstract: Nearly 50% of patients who are diagnosed with locally advanced cervical cancer have an unfavorable pathological response to conventional treatment. MicroRNAs (miRNAs) are potential biomarkers in cervical cancer; however, their role in identifying patients who do not respond to conventional treatment remains poorly investigated. Here, we identify a set of miRNAs that can be used as molecular markers to predict the pathological response in locally advanced cervical cancer patients receiving radiation and chemotherapy treatment.
  
  
  
  Forty-one patients diagnosed with locally advanced cervical cancer were invited to participate in this study and enrolled after they signed an informed consent. Two patient cohorts were randomized for miRNA expression profiling, a discovery cohort (n=10) and a validation cohort (n=31); profiling was performed by means of a miScript miRNA PCR Array. After a median clinical follow-up of 45months, statistical analysis was performed to identify miRNAs that could discriminate non-responders from complete pathological responders to conventional treatment.
  
  
  
  miRNA expression profiling identified 101 miRNAs that showed significant differences between non-responders and complete pathological responders (p<0.05). Seven differentially expressed miRNAs were selected, and their expression patterns were confirmed in the validation phase; thus, miR-31-3p, -3676, -125a-5p, -100-5p, -125b-5p, and -200a-5p and miR-342 were significantly associated with clinical response. Expression of this miRNA signature above the median level was a significant predictor of non-response to standard treatment (p<0.001).
  
  
  
  These seven validated miRNA signatures could be used as molecular biomarkers of chemo- and radio-resistance in locally advanced cervical cancer patients.
authors.affiliation: Instituto Nacional de Cancerología, Laboratorio de Genómica, Ciudad de México, Mexico; Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biologicas, Departmanento de Microbiología, Ciudad de México, Mexico.
authors.forename: Abraham
authors.initials: A
authors.lastname: Pedroza-Torres
authors.affiliation: Instituto Nacional de Cancerología, Laboratorio de Genómica, Ciudad de México, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Fernández-Retana
authors.affiliation: Direccion de Infecciones Crónicas y Cáncer, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Peralta-Zaragoza
authors.affiliation: Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Ciudad de México, Mexico.
authors.forename: Nadia
authors.initials: N
authors.lastname: Jacobo-Herrera
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Ciudad de México, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Cantú de Leon
authors.affiliation: Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biologicas, Departmanento de Microbiología, Ciudad de México, Mexico.
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Cerna-Cortés
authors.affiliation: Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México., Mexico.
authors.forename: Cesar
authors.initials: C
authors.lastname: Lopez-Camarillo
authors.affiliation: Instituto Nacional de Cancerología, Laboratorio de Genómica, Ciudad de México, Mexico; Universidad Nacional Autónoma de México UNAM, FES-Iztacala, UBIMED, Tlalnepantla, Estado de México, Mexico. Electronic address: carlos.pplas@gmail.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Plasencia
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001918:Brachytherapy; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011897:Random Allocation; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D002945:Cisplatin