Expression and Clinical Significance of Sideroflexin 4 (SFXN4) in Colorectal Cancer

Sideroflexin 4 (SFXN4) is important for mitochondrial function and relatively unstudied in relation to cancer. The aim of the study was to examine the SFXN4 gene and protein expression in patients with colorectal cancer (CRC) to identify associations with various clinicopathological parameters and evaluate the diagnostic and prognostic significance.

SFXN4 protein and mRNA expression in cancer and paired normal tissues was determined in patients with CRC using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR. Immunohistochemical staining was used to study the cell type origin of the SFXN4 expression. SFXN4 was silenced in HT-29 cells and several genes known to be involved in colorectal carcinogenesis were examined on mRNA level by RT-qPCR.

The protein and mRNA level of SFXN4 was 35 and 19% higher in tumor tissue compared to those in normal paired tissue (p<0.05). Non-mucinous type expressed 21% higher protein level compared to levels in the mucinous type (p<0.05). Immunohistochemistry revealed SFXN4 cytoplasmic staining mainly in the epithelial cells in cancer and normal tissue. A 19% higher SFXN4 mRNA level was observed in smaller tumors and in left colon compared to right colon cancer (p<0.05). Silencing of SFXN4 in HT-29 cells resulted in an up-regulation of IL-8 by 63% and increased proliferation (p<0.05).

The findings indicate the importance of SFXN4 in colorectal carcinogenesis and extended studies are necessary to elucidate its role as a prognostic biomarker.