Connecting concentrations of copper, selenium, and zinc with transcriptomic and proteomic data of well-characterized human colorectal cancer cell lines

Abstract

Background

Colorectal cancer (CRC) incidence is associated with lower circulating selenium and zinc and elevated copper concentrations. Moreover, copper and selenium accumulate within tumor tissue, indicating a disturbed homeostasis of these essential trace elements in CRC.

Objective

This study aimed to identify associations between CRC characteristics (based on genomic, transcriptomic and proteomic data) and trace element concentrations.

Methods

The concentrations of copper, selenium, and zinc were measured in 83 human CRC cell lines and correlated with transcript and protein expression levels to identify trace element-related gene signatures. By using publicly available gene expression data from The Cancer Genome Atlas we investigated the association between those signatures with the survival probability of CRC patients.

Results

The CRC cell lines differed in their copper (fold change 7.3), selenium (fold change 6), and zinc (fold change 2.6) concentrations. The concentrations were not associated with genetic or cellular characteristics, except for lower copper concentrations in KRAS mutant cells. Expression levels of known copper- and zinc-related proteins correlated significantly with the respective trace element concentrations, serving as a proxy for trace element concentrations in tumors, and with patient survival. This was not the case for selenium and selenoproteins. In addition, an unbiased approach identified novel high and low copper- and zinc-related gene expression signatures significantly associated with patient’s outcome.

Conclusion

Herein we identify gene signatures associated with intracellular copper and zinc concentrations in CRC cell lines. Extrapolating these signatures to primary colorectal tumors revealed that they can inform outcome of CRC patients.