A8

Cervical cancer is one of the most common gynecologic malignancy in Hong Kong. The identification of pretreatment markers with predictive significance for the presence of lymph node metastasis in low stage of cervical cancer is clinically important. MicroRNAs (miRNAs) are noncoding RNA molecules of 21 to 24 nt that regulate the expression of target genes in a post-transcriptional manner. Recent evidence indicates that miRNAs play essential roles in tumorigenesis and cancer metastasis. This study was to evaluate the deregulated miRNAs associated with cervical cancer metastasis. A total of 20 cervical squamous cell carcinomas, in which 10 had pathologically confirmed lymph node metastasis and 10 no metastasis, were included in the study. RNAs were extracted from microdissected tumor tissue specimens. Real-time reverse transcription PCR technology-based miRNA array enabling quantitation of 365 human mature miRNAs, was used to profile global miRNA expression in cervical cancer. dChip software was used for biostatistical analysis of data. Global miRNA expression data obtained from all 20 arrays were normalized, and then the corresponding model-based expression index was calculated. Unsupervised hierarchical clustering analysis of data showed a distinct separation between cancers in the presence and absence of lymph node metastasis. Supervised hierarchical clustering analysis revealed that of 13 significantly differentially expressed miRNAs, 10 miRNAs including miR-137 (4.76-fold), miR-203 (3.82-fold), miR-594 (3.58-fold), miR-149 (3.05-fold), mir-365 (2.61-fold), miR-556 (2.43-fold), miR-33 (2.32-fold), miR-627 (2.12-fold), miR-20a (2.05-fold) and mir-653 (2.04-fold) were up-regulated and 3 miRNAs including miR-187 (-4.31), miR-4095p (-2.65-fold) and miR-615 (-2.1-fold) were down-regulated in the cervical squamous cell carcinomas with lymph node metastasis compared to that without metastasis. The results obtained from this preliminary study indicate that the deregulation of miRNAs appears to be involved in the cervical cancer progression, and miRNA expression signature can be of potential importance as predictive biomarker in cervical cancer metastasis. Further validation of such microRNA pattern by the testing set and an independent cohort of patients with cervical cancer as well as the functional study of these deregulated miRNAs are ongoing.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A8.

Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC