Sen-Lin Xu1, Dong-Zu Zeng2, Wei-Guo Dong3, Yan-Qing Ding4, Jun Rao5, Jiang-Jie Duan1, Qing Liu1, Jing Yang1, Na Zhan6, Ying Liu1, Qi-Ping Hu1, Xia Zhang1, You-Hong Cui1, Hsiang-Fu Kung1, Shi-Cang Yu1, Xiu-Wu Bian1. 1. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University Chongqing 400038, China ; Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Third Military Medical University Chongqing 400038, China. 2. Department of General Surgery, Southwest Hospital, Third Military Medical University Chongqing 400038, China. 3. Department of Gastroenterology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, China. 4. Department of Pathology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong Province, China. 5. Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Third Military Medical University Chongqing 400038, China. 6. Department of Pathology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, China.
Abstract
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. METHODS AND 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. 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. METHODS AND 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. 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.
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