Tissue and Serum miRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment

• Published in: PloS one 2016, Vol.11 (4), p.e0152032
• Main Authors: Al-Khanbashi, Manal, Caramuta, Stefano, Alajmi, Adil M, Al-Haddabi, Ibrahim, Al-Riyami, Marwa, Lui, Weng-Onn, Al-Moundhri, Mansour S
• Format: Article
• Language: English
• Subjects: Adjuvant chemotherapy; Adult; Analysis; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biology and life sciences; Biomarkers; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Cancer; Cancer therapies; Care and treatment; Cell cycle; Chemotherapy; Chemotherapy, Adjuvant; Colorectal cancer; Cyclophosphamide; Cyclophosphamide - administration & dosage; Development and progression; Diagnosis; Docetaxel; Doxorubicin; Doxorubicin - administration & dosage; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Health sciences; Hospitals; Humans; Medical diagnosis; Medical prognosis; Medical research; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miRNA; Neoadjuvant Therapy; Neoplasm Staging; Non-coding RNA; Oligonucleotide Array Sequence Analysis; Oncology; Pathology; Patients; Polymerase chain reaction; Prognosis; Real-Time Polymerase Chain Reaction; Ribonucleic acid; RNA; Serum levels; Statistical analysis; Statistical methods; Studies; Surgery; Survival; Survival Rate; Taxoids - administration & dosage; Trastuzumab - administration & dosage; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152032

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. 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. 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. Variations in serum miRNA levels during NAC treatment may be therapeutically significant for predicting response and survival outcomes.