title: Tissue and Serum miRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are small non-coding RNA that plays a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes.
  
  
  METHODS
  Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, and Spearman, Wilcoxon signed-ranks tests. P≤0.05 was considered statistically significant.
  
  
  RESULTS
  We analyzed 72 tissue samples and 108 serum samples from 9 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. This is one of the early reports on miR-3200 in response to treatment in breast cancer, as serum levels of miR-3200 found to decline during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates at time of diagnosis.
  
  
  CONCLUSIONS
  Variations in serum miRNA levels during NAC treatment may be therapeutically significant for predicting response and survival outcomes.
authors.affiliation: Medical Oncology Unit, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Manal
authors.initials: M
authors.lastname: Al-Khanbashi
authors.affiliation: Department of Oncology-Pathology, Karolinska institute, Cancer Center Karolinska, Karolinska University Hospital-Solna, Stockholm, Sweden.
authors.forename: Stefano
authors.initials: S
authors.lastname: Caramuta
authors.affiliation: Department of Surgery, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Adil M
authors.initials: AM
authors.lastname: Alajmi
authors.affiliation: Department of Pathology, College of Medicine, Sultan Qaboos University, Muscat, Oman.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al-Haddabi
authors.affiliation: Department of Pathology, College of Medicine, Sultan Qaboos University, Muscat, Oman.
authors.forename: Marwa
authors.initials: M
authors.lastname: Al-Riyami
authors.affiliation: Department of Oncology-Pathology, Karolinska institute, Cancer Center Karolinska, Karolinska University Hospital-Solna, Stockholm, Sweden.
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
authors.affiliation: Medical Oncology Unit, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Mansour S
authors.initials: MS
authors.lastname: Al-Moundhri
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D000068878:Trastuzumab