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Purpose  Colon cancer (CC) is a very common gastrointestinal tumor that is prone to invasion and metastasis in the late stage. This study aims to observe the expression of Na + /Ca 2+  exchangers (NCXs) and analyze the correlation between NCXs and the prognosis of CC.    Methods  Specimens of 111 stage II–IV CC patients were collected. We used western blotting, qPCR, and immunohistochemical staining to observe the distributions and expression levels of NCX isoforms (NCX1, NCX2, and NCX3) in CC and distal normal tissues. Cox proportional hazards models were used to assess prognostic factors for patients.    Results  The expression of NCXs in most tumor specimens was lower than that in normal tissues. The NCX expression levels in tumor tissues from the primary tumor, local lymph node metastasis sites, and distant liver metastasis sites were increasingly significantly lower than those in normal tissues. The results of the Kaplan-Meier survival curves showed that the downregulation of any NCX isoform was closely related to the worse prognosis of advanced CC.    Conclusion  NCXs can be used as independent prognostic factors for CC. Our research results are expected to provide new targets for the treatment of CC.

The downregulation of NCXs is positively correlated with the prognosis of stage II–IV colon cancer