Methylated claudin-11 associated with metastasis and poor survival of colorectal cancer.
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ABSTRACT:
SUBMITTER: Li J
PROVIDER: S-EPMC5707097 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAldehyde dehydrogenase 1A1 (ALDH1A1) encodes an enzyme that oxidizes aldehydes to their corresponding carboxylic acids. In colorectal cancer ALDH1A1 marks cancer stem cells and plays putative roles in tumor progression and drug resistance. However, the potential value of ALDH1A1 as a diagnostic marker or target for therapy remains unclear. Here, we have analyzed ALDH1A1 mRNA and protein levels in relation to clinical, histopathological and molecular tumor features in large series of human colorectal cancer.MethodsALDH1A1 protein levels were determined by immunohistochemistry in a series of primary colorectal tumors and their corresponding liver metastases (n = 158). ALDH1A1 mRNA levels were analyzed in several large patient cohorts of colorectal cancer. ALDH1A1 mRNA and protein levels were then related to overall survival and to clinical, histopathological and molecular tumor features.ResultsHigh levels of ALDH1A1 were associated with a poorly differentiated histology and a right-sided tumor location, but not to a mesenchymal-like molecular subtype. Liver metastases contained significantly higher levels of ALDH1A1 compared to the corresponding primary tumors. Radio- and/or chemotherapy prior to tumor resection was associated with increased ALDH1A1 levels regardless of the molecular subtype. Finally, ALDH1A1 protein expression in primary tumors and metastases correlated with shorter overall survival.ConclusionsALDH1A1 expression is associated with features of poor prognosis, including a poorly differentiated histology and 'right-sidedness' of the primary tumor, and with shorter overall survival. ALDH1A1 is also highly expressed in therapy-surviving tumors and in liver metastases. These results warrant further research into the potential value of targeting ALDH1A1 in order to improve the efficacy of standard treatment and thereby preventing tumor recurrence.
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Project description:The present study was to investigate the clinical significance of peroxiredoxin 2 (PRDX2), an oncoenzyme, in the development and progression of colorectal cancer(CRC).We found levels of PRDX2 mRNA and protein were higher in CRC cell lines than in normal human colonic epithelial cells. PRDX2 expression was significantly up-regulated in CRC lesions compared with that in the adjacent noncancerous tissues. CRC tissues from 148 of 226 (65.5%) patients revealed high level of PRDX2 protein expression in contrast to only 13 of 226 (5.8%) PRDX2 strong staining cases in the adjacent noncancerous tissues. Increased expression of PRDX2 protein was significantly associated with poor tumor differentiation (p = 0.001), advanced local invasion (p = 0.046), increased lymph node metastasis (p = 0.008), and advanced TNM stage (p = 0.020). Patients with higher PRDX2 expression had a significantly shorter disease-free survival and worse disease-specific survival than those with low expression. Importantly, PRDX2 up-regulation was an independent prognostic indicator for stage I-III, early stage (stage I-II) and advanced stage (stage III) patients. In conclusion, our findings suggest PRDX2 up-regulation correlates with tumor progression and could serve as a useful marker for the prognosis of CRC.
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