5-6-7-8-tetrahydrofolic-acid and Neoplasm-Metastasis

Protein/nucleic acid deglycase DJ‑1 (DJ‑1) is a 20‑kDa conserved protein, which belongs to the DJ‑1/ThiJ/Pfp Ⅰ protein superfamily. Immunohistochemistry was performed to investigate the expression of DJ‑1 in a colorectal cancer (CRC) tissue microarray containing tumor and corresponding adjacent normal tissues. In the present study, DJ‑1 expression was significantly upregulated in CRC cells and tissues, compared with that in normal colon cells and adjacent normal tissues, respectively. In addition, patients with high DJ‑1 expression levels had a worse overall survival (OS) compared with patients with low expression levels. Multivariate Cox regression analysis revealed that high DJ‑1 expression levels was an independent prognostic factor for patients with CRC. Moreover, DJ‑1 was able to regulate the PI3K/Akt/p27/cyclin E and PI3K/Akt/mTOR signaling pathways to promote CRC cell growth and metastasis in vitro and in vivo. In addition, DJ‑1 regulated the NF‑κB/Snail signaling pathway to induce CRC cell epithelial‑mesenchymal transition to promote migration and invasion. Notably, patients receiving LFP treatment (oxaliplatin, 5‑FU and tetrahydrofolate) had an increased OS compared with patients who underwent only surgery and low DJ‑1 expression levels. The findings from the present study suggest that DJ‑1 may serve as a promising prognostic marker and predicts chemotherapy efficacy in patients with CRC.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; HCT116 Cells; HT29 Cells; Humans; Male; Mice; Middle Aged; Neoplasm Metastasis; Oxaliplatin; Prognosis; Protein Deglycase DJ-1; Signal Transduction; Survival Analysis; Tetrahydrofolates; Up-Regulation; Xenograft Model Antitumor Assays