title: Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Sen-Lin
authors.initials: SL
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Southwest Hospital, Third Military Medical University Chongqing 400038, China.
authors.forename: Dong-Zu
authors.initials: DZ
authors.lastname: Zeng
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Dong
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong Province, China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ding
authors.affiliation: Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Third Military Medical University Chongqing 400038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Rao
authors.affiliation: 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.
authors.forename: Jiang-Jie
authors.initials: JJ
authors.lastname: Duan
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhan
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Qi-Ping
authors.initials: QP
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.affiliation: 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.
authors.forename: Shi-Cang
authors.initials: SC
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000032:analysis / Q000096:biosynthesis*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D050697:Retinal Dehydrogenase
chemical_list: D014408:Biomarkers, Tumor; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: Colorectal carcinoma; aldehyde dehydrogenase 1A1; metastasis; prognosis; β-catenin