Downregulation of circulating <i>miR-22</i> and elevation of serum ATP-citrate lyase in colorectal cancer: a proof-of-concept study
MOLECULAR BIOLOGY REPORTS, cilt.53, sa.1, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 53 Sayı: 1
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s11033-026-12531-1
- Dergi Adı: MOLECULAR BIOLOGY REPORTS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Gazi Üniversitesi Adresli: Evet
Özet
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 (rho = -0.362; p = 0.004), but not within the patient group (rho = -0.128; p = 0.485) or within controls (rho = -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.