Abstract
BackgroundCarbonic anhydrases (CAs) have been implicated in the pathogenesis of human cancers. Carbonic anhydrase VII (CA7), a member of the CA gene family, was recently demonstrated to be expressed in several human tissues including colon. Nevertheless, the expression and clinical relevance of CA7 in colorectal carcinoma (CRC) has not been investigated.MethodsReal-time PCR, western blot, and immunohistochemistry analyses were used to determine CA7 expression in CRC clinical samples. The correlation of CA7 expression with clinicopathologic features was assessed in 228 patients from Luoyang, China (training cohort) and validated in 151 patients from Shanghai, China (validation cohort). Kaplan-Meier and Cox proportional regression analyses were used to estimate the association between CA7 expression and patients’ survival.ResultsCA7 expression was frequently downregulated in CRC tissues at both the mRNA and protein levels. Reduced expression of CA7 was significantly correlated with poor differentiation, positive lymph node metastasis, advanced TNM stage and unfavorable clinical outcome not only in the training cohort but also in the validation set. Survival analysis indicated that patients with lower CA7 expression had a significantly shorter disease-specific survival (DSS) than those with higher CA7 expression. Importantly, further stage-based analyses revealed that decreased CA7 expression significantly predicted poor DSS and was an independent adverse prognostic indicator for patients with early stage tumors in both cohorts.ConclusionsOur results indicate that decreased expression of CA7 correlates with disease progression and predicts poor prognosis in CRC, especially for patients with early stage tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1216-y) contains supplementary material, which is available to authorized users.
Highlights
Carbonic anhydrases (CAs) have been implicated in the pathogenesis of human cancers
Western blot analysis from an independent set of 25 paired CRC and adjacent normal specimens demonstrated that protein expression of Carbonic anhydrase VII (CA7) was significantly downregulated in tumor tissues compared with adjacent normal tissues (18/25, p < 0.001, Figure 1B)
To further investigate the phenotypic expression patterns of CA7 protein in CRC tissues, IHC analysis was performed in 228 specimens of patients from the training cohort
Summary
Carbonic anhydrases (CAs) have been implicated in the pathogenesis of human cancers. Carbonic anhydrase VII (CA7), a member of the CA gene family, was recently demonstrated to be expressed in several human tissues including colon. The expression and clinical relevance of CA7 in colorectal carcinoma (CRC) has not been investigated. Colorectal carcinoma (CRC) is one of the leading causes of cancer-related death globally, accounting for more than 1.2 million new cases and 600,000 deaths per year [1,2]. Due to post-surgical recurrence and fatal distant metastasis, the Carbonic anhydrases (CAs) are a family of ubiquitously expressed metalloenzymes that catalyze the reversible conversion of carbon dioxide to bicarbonate and proton [5].
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