MicroRNA expression profiles of esophageal cancer

Department of Pathology, Mount Sinai Medical Center, New York, NY 10029, USA.
The Journal of thoracic and cardiovascular surgery (Impact Factor: 3.41). 03/2008; 135(2):255-60; discussion 260. DOI: 10.1016/j.jtcvs.2007.08.055
Source: PubMed

ABSTRACT Expression of microRNAs by array analysis provides unique profiles for classifying tissues and tumors. The purpose of our study was to examine microRNA expression in Barrett esophagus and esophageal cancer to identify potential markers for disease progression.
MicroRNA was isolated from 35 frozen specimens (10 adenocarcinoma, 10 squamous cell carcinoma, 9 normal epithelium, 5 Barrett esophagus, and 1 high-grade dysplasia). MicroRNA expression was analyzed with Ambion bioarrays (Ambion, Austin, Tex) containing 328 human microRNA probes.
Unsupervised hierarchic clustering resulted in four major branches corresponding with four histologic groups. One branch consisted of 7 normal epithelium samples and 1 squamous cell carcinoma sample. The second branch consisted of 7 squamous cell carcinoma samples and 1 normal epithelium sample. The third branch contained 4 Barrett esophagus samples and 1 squamous cell carcinoma sample. The fourth contained all the adenocarcinoma samples and 1 sample each of Barrett esophagus, normal epithelium, squamous cell carcinoma, and high-grade dysplasia. Supervised classification with principal component analysis determined that the normal epithelium samples were more similar to the squamous cell carcinoma tumors, whereas the Barrett esophagus samples were more similar to adenocarcinoma. Pairwise comparisons between sample types revealed microRNAs that may be markers of tumor progression. Both mir_203 and mir_205 were expressed 2- to 10-fold lower in squamous cell carcinoma and adenocarcinomas than in normal epithelium. The mir_21 expression was 3- to 5-fold higher in both tumors than in normal epithelium. Prediction analysis of microarray classified 3 Barrett esophagus samples as Barrett esophagus, 1 as adenocarcinoma, and 1 as normal epithelium.
Expression profiles of miRNA distinguish esophageal tumor histology and can discriminate normal tissue from tumor. MicroRNA expression may prove useful for identifying patients with Barrett esophagus at high risk for progression to adenocarcinoma.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The dismal outcome of laryngeal squamous cell carcinoma (SCC) patients highlights the need for novel prognostic biomarkers. The involvement of microRNAs in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated. We sought to identify microRNAs that exhibit altered expression in laryngeal SCC and to determine whether microRNA (miRNA) expression is predictive of disease progression and/or patient survival. The expression of two miRNAs, miR-21 and miR-375, was evaluated using total RNA isolated from freshly-frozen primary tumors and non-cancerous laryngeal squamous epithelial tissues and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. We further analyzed the association between the expression of miRNAs and the clinicopathological features. A marked difference in the microRNA expression pattern was observed between tumors and non-cancerous tissue. MiR-21 and miR-375 were expressed at higher and lower levels, respectively, in the laryngeal SCC samples, compared to the normal samples (p < 0.01 and p < 0.001, respectively). There was no correlation between characteristics such as age, sex, clinical stage, and alcohol use, and the expression level of mir-21. The relative expression of mir-375 in laryngeal SCC was shown to be associated with localization of the tumor in these patients (p = 0.037) and with alcohol use (p < 0.05). Patients with high miR-21 or low miR-375 expression in tumor tissues had poorer prognoses compared to patients with lower miR-21 or higher miR-375 expression. Furthermore, the miR-21/miR-375 expression ratio was highly sensitive (0.94) and specific (0.94) for disease prediction. These data suggest that the pattern of microRNA expression in primary laryngeal SCC tissues is reflective of the disease status and that miR-21 and miR-375 expression levels, in particular, may serve as potential biomarkers with applications in the clinical setting.
    American Journal of Translational Research 01/2014; 6(5):604-13. · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic influences, such as DNA methylation, histone acetylation, and up-regulation/down-regulation of genes by microRNAs, change the genetic makeup of an individual without affecting DNA base-pair sequences. Indeed, epigenetic changes play an integral role in the progression from normal esophageal mucosa to Barrett's esophagus to esophageal adenocarcinoma via dysplasia-metaplasia-neoplasia sequence. Many genes involved in esophageal adenocarcinoma display hypermethylation, leading to their down-regulation. The classes of these genes include cell cycle control, DNA and growth factor repair, tumor suppressors, antimetastasis, Wnt-related genes, and proapoptotic genes. Histone acetylation in the pathophysiology of esophageal diseases has not been thoroughly investigated, and its critical role in the development of esophageal adenocarcinoma is less defined. Many microRNAs have been associated with the development of Barrett's esophagus and esophageal adenocarcinoma. Here, we critically addressed the specific steps most closely influenced by microRNAs in the progression from Barrett's esophagus to esophageal adenocarcinoma. However, microRNAs can target up to hundreds of genes, making it difficult to correlate directly with a given phenotype of the disease. Esophageal adenocarcinoma progressing from premalignant condition of Barrett's esophagus carries an extremely poor prognosis. Risk stratification for patients based on their epigenetic profiles may be useful in providing more targeted and directed treatment to patients.
    Clinical and Translational Science 11/2014; DOI:10.1111/cts.12242 · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNA-93-5p (miR-93) is a novel oncogenic microRNA (miRNA) and is elevated in diverse human malignancies. Aberrant expression and dysfunction of miR-93 are involved in many types of human tumours. However, the exact role of miR-93 remains unclear in head and neck squamous cell carcinoma (HNSCC). The objective of this study is to determine the expression pattern and clinical significance of miR-93 in HNSCC. MiR-93 expression levels in 103 primary HNSCC tissues and 16 corresponding non-cancerous epithelia were analysed by miRNA in situ hybridisation and correlated with the clinicopathological parameters and patient outcomes. Moreover, the expression of miR-93 was examined in four HNSCC cell lines and 17 pairs of HNSCC tissues and their corresponding adjacent tissues using quantitative real-time PCR (qRT-PCR). The miR-93 levels in HNSCC tissues and cell lines were significantly higher than those in the non-cancerous tissues. Notably, high miR-93 expression was significantly associated with T classification, lymph node metastasis and clinical stage. Kaplan-Meier survival analysis demonstrated that patients with high miR-93 expression had poorer overall survival than patients with low miR-93 expression. Multivariate Cox regression analysis revealed that miR-93 overexpression and lymph node metastasis were independent prognostic factors in patients with HNSCC. This study demonstrated that miR-93 expression was significantly increased in HNSCC tissue samples and cell lines and that miR-93 overexpression was associated with tumour progression, metastasis and poor prognosis in HNSCC patients. These results suggest that miR-93 may play a critical role in the initiation and progression of HNSCC, indicating that miR-93 may be a valuable marker for the prediction of metastasis and prognosis in HNSCC.
    Tumor Biology 01/2015; DOI:10.1007/s13277-015-3038-6 · 2.84 Impact Factor

Full-text (2 Sources)

Available from
Jun 4, 2014