Downregulation of circulating miR-22 and elevation of serum ATP-citrate lyase in colorectal cancer: a proof-of-concept study.

BACKGROUND

Colorectal cancer (CRC) involves metabolic reprogramming alongside genetic alteration. ATP-citrate lyase (ACLY), the rate-limiting enzyme of de novo lipogenesis, is a validated target of microRNA-22 (miR-22) in tumor tissue. We asked whether both are dysregulated in the circulation of patients with CRC and whether they carry diagnostic value.

METHODS AND

RESULTS

Serum ACLY (ELISA) and circulating miR-22 (RT-qPCR, normalized to U6) were measured in 32 patients with histopathologically confirmed CRC and 31 healthy controls; metabolic activity was assessed by PET/CT SUVmax. Analyses used SPSS and REST 2009. miR-22 was downregulated in patients (relative expression 0.175; p < 0.001) and serum ACLY was elevated (p = 0.009). Across the whole cohort the two markers were inversely correlated (ρ = -0.362; p = 0.004), but not within the patient group (ρ = -0.128; p = 0.485) or within controls (ρ = -0.180; p = 0.333), indicating that it reflects their opposite direction of change between groups. Serum ACLY was higher in patients with radiologically active tumor involvement on PET/CT (p = 0.047). The ACLY/miR-22 ratio separated patients from controls with an AUC of 0.984 (p < 0.001), exceeding serum ACLY alone (AUC = 0.691).

CONCLUSIONS

In this single-center, proof-of-concept study, circulating miR-22 and serum ACLY were dysregulated in opposite directions in colorectal cancer, and their ratio discriminated patients from controls (AUC > 0.98). These estimates were obtained in a single-center discovery cohort without an independent validation set and require external validation before any diagnostic use. The data do not demonstrate a direct regulatory interaction between the two markers in the circulation, and require validation in larger, prospective cohorts.