Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma

ALDH1A1 表达的不同模式可预测结直肠癌的转移和不良预后

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作者:Sen-Lin Xu, Dong-Zu Zeng, Wei-Guo Dong, Yan-Qing Ding, Jun Rao, Jiang-Jie Duan, Qing Liu, Jing Yang, Na Zhan, Ying Liu, Qi-Ping Hu, Xia Zhang, You-Hong Cui, Hsiang-Fu Kung, Shi-Cang Yu, Xiu-Wu Bian

Conclusion

Our results indicate that RA/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC.

Purpose

Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC.

Results

In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as RA/C and found that the capabilities of tumor invasion and metastasis in the tumors with RA/C < 1 were significantly higher than those with RA/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with RA/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with RA/C < 1 and ALDH1A1(high) expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis.

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