Dicer and miRNA in relation to clinicopathological variables in colorectal cancer patients

Dicer 和 miRNA 与结直肠癌患者临床病理变量的关系

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作者:Johannes Stratmann, Chao-Jie Wang, Sebastian Gnosa, Asa Wallin, David Hinselwood, Xiao-Feng Sun, Hong Zhang

Background

Dicer is aberrantly expressed in several types of cancers. Applying real-time PCR, we detected the expression of Dicer mRNA in normal mucosa (n = 162), primary colorectal cancer (CRC) (n = 162) and liver metastasis (n = 37), and analysed the relationship between Dicer expression and clinicopathological features. We also correlated the expression of Dicer mRNA to the miRNA expression of miR-141, miR-200a, miR-200b, mir-200c and miR-429 in liver metastases.

Conclusion

Dicer is up-regulated in the early development of rectal cancers. An increased expression of Dicer mRNA in normal mucosa from CRC patients is significantly related to poor survival independently of gender, age, tumour site, stage and differentiation.

Methods

RT-PCR and qPCR were used to analyse the Dicer expression in normal mucosa, primary tumour and liver metastasis by using the High Capacity cDNA Reverse Transcription Kit and TaqMan™® Gene Expression assays for Dicer and GAPDH. RT-PCR and qPCR were used to detect miRNA expression in liver metastases by utilizing TaqMan® MicroRNA Reverse Transcription Kit and TaqMan® miRNA Assays. Statistical analyses were performed with STATISTICA.

Results

Dicer expression in rectal cancer (3.146 ± 0.953) was higher than in colon cancer (2.703 ± 1.204, P = 0.018). Furthermore the Dicer expression was increased in primary tumours (3.146 ± 0.952) in comparison to that in normal mucosa from rectal cancer patients (2.816 ± 1.009, P = 0.034) but this is not evident in colon cancer patients. Dicer expression in liver metastases was decreased in comparison to that of either normal mucosa or primary tumour in both colon and rectal cancers (P < 0.05). Patients with a high Dicer expression in normal mucosa had a worse prognosis compared to those with a low Dicer expression, independently of gender, age, tumour site, stage and differentiation (P < 0.001, RR 3.682, 95% CI 1.749 - 7.750). In liver metastases, Dicer was positively related to miR-141 (R = 0.419, P = 0.015).

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