Exploring the Clinical Significance of Circulating H19 lncRNA and IGF-2 mRNA in Colorectal Carcinoma

Despite effective screening programs, colorectal cancer (CRC) continues to be an important health burden. Circulating RNAs of various types, which are relatively stable in bodily fluids, have been explored as cancer biomarkers with proven potential in detection, diagnosis, treatment, and patient follow-up, in various cancer types, including CRC. Here, we were interested in the clinical significance of H19 and insulin-like growth factor 2 (IGF2) as circulating RNA biomarkers in CRC, two imprinted genes of the IGF-2/H19 cluster.

H19 lncRNA and IGF-2 mRNA were quantified in plasma samples of 80 pathologically confirmed, treatment-naïve CRC patients, and 80 CRC-free control subjects, of whom 40 had polyps and 40 others did not.

Plasma levels of H19 lncRNA and IGF-2 mRNA were significantly higher in CRC patients than in control subjects; relative median values of H19 lncRNA were 912, 97, and 262 in CRC patients, the polyp controls, and non-polyp controls, respectively (p=0.000135 and p=0.002, respectively). Relative median values of plasma IGF-2 mRNA were 298, 29, and 112 in the above groups, respectively (p<0.001 and p=0.035, respectively. Patients with lymph node metastases had significantly higher H19 lncRNA levels than patients without lymphatic metastases (median values 1474 vs. 196; p=0.05). This association was absent for IGF-2 mRNA. Although not statistically significant, both RNA markers showed a tendency to be associated with larger tumor size and advanced disease stage.

Plasma H19 lncRNA and IGF-2 mRNA may be a marker of tumor burden in CRC, while H19 lncRNA is also an indicator of CRC progression, which, if confirmed, can be used in the clinical management of CRC patients.