Differential MicroRNA Expression in Breast Cancer with Different Age-Onset

• Main Authors: Chien Fang Li, 李建芳
• Other Authors: L. L. Hsieh
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/68794644232199518030

碩士 === 長庚大學 === 生物醫學研究所 === 98 === Purpose It has been shown that the median age at diagnosis of breast cancer in Taiwan (45-49 years) was younger than western countries (70-74 years). Many studies have reported that young breast cancer patients had poorer prognosis than old patients. Expressions of microRNAs (miRNAs) have been found to play critical roles in the process of tumor initiation and progression. This study was therefore designed to explore the miRNAs expression profile in Taiwanese breast tumors with different age-onset. In addition, the associations between miRNAs and clinicopathological parameters were also evaluated. Materials and Methods This study was carried out by a two-stage experimental design. At stage I, candidate miRNAs were selected either from a miRNA microarray analysis on 12 breast tissues (6 tumors and 6 normal adjacent tissues) from Taiwanese young breast cancer patients (age < 35 y/o) or from literature reviews. At stage II, the expression of candidate miRNAs was analyzed on 285 breast tissues from 150 breast cancer patients (<35y/o, n=12; 36-40y/o, n=44; 41-50y/o, n=46; >51y/o, n=48) by Q-PCR. All of them had received curative operation in Chang Gung Memorial Hospital and only those without metastatic disease and did not receive neoadjuvant chemotherapy were included in the present analysis. The expression levels of miRNAs were first normalized by Partek shift median models and then analyzed by 2 way ANOVA. To eliminate the effects of multiple comparisons, a false discovery rate (FDR) was also calculated. Results To minimize the number of false-positive findings, only a p < 0.05 with a FDR less than 5% was considered to be statistically significant. There were 6 miRNAs (miR-21, miR-141, miR-145, miR-200a, miR-200c, and miR-335) expressed commonly significant difference between tumor and normal tissues. Among them, miR-335 and miR-145 were down-regulated in breast tumors, while miR-21, miR-200a, miR-200c, and miR-141 were up-regulated. Besides, 3 up-regulated (miR-96, miR-182, and miR-183) and 8 down- regulated (miR-10a, miR-10b, miR-125b, miR-127-3p, miR-130a, miR-143, miR-19, and miR-320) miRNAs were identified in very young breast tumors (age < 35 y/o). For young breast tumors (36-40 y/o), 3 up-regulated (miR-30b, miR-30d, and miR-149) and 3 down- regulated (miR-487b, miR-548c-5p, and miR-181d) miRNAs were found. Only one down- regulated (miR-206) miRNA was observed in premenopausal breast tumors (41-50 y/o) and no unique miRNA was found for postmenopausal tumors (age > 51 y/o). Furthermore, MiR-375 and miR-17 was up-regulated in ER positive and negative tumors, respectively; MiR-9 and miR-205 was down-regulated in PR positive and negative tumors, respectively. MiR-30c was over-expressed in HER2 negative breast tumors. MiR-375 and miR-29c were over-expressed in luminal B type tumors, but down-regulated in HER2 positive breast tumors. MiR-532-5p was over expressed in triple-negative breast tumors. Conclusion This study demonstrated that altered expression of distinct miRNAs in breast tumors with different age-onset and molecular phenotype were existed. This information will provide clues for future study on molecular networks involved in specific age-onset and phenotypic breast cancers in Taiwan.