MicroRNA expression in tissue and circulating tumor cells of patients with stage II-IV colon cancer.
Authors: Novikova Inna A. , Zlatnik Elena Yu , Gvaldin Dmitry Yu. , Pushkin Anton A. , Gevorkyan Yuriy A. , Soldatkina Natalya V. , Petrov Dmitriy S. , Kolesnikov Vladimir E. , Savchenko Dmitriy A. , Tolmakh Roman E. , Dashkov Andrey V. , Katelnitskaya Oksana V. , Ilchenko Sergei A. , Kaymakchi Oleg Yu. , Kit Oleg I. , Dzhenkova Elena A. , Kolesnikov Evgeniy N. , Maksimov Aleksey Yu. , Shaposhnikov Aleksandr V. 
Published: June 2022

e15502

Background: The purpose of this study was a comparative analysis of the expression of miRNAs in the tumor and circulating tumor cells (CTCs) in colon cancer (CC). Methods: Expression of seven miRNAs (hsa-let-7i-5p, hsa-miR-126-5p, hsa-miR-143-3p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-26a-5p, hsa-miR-92a-3p) were determined by real-time PCR in tumors of 200 patients with stage II-IV CC compared with normal colon tissue; levels of CTCs were determined by the CellSearch, and at CTC > 3, CTCs were isolated and the expression of the same miRNAs was studied in them. Results: Tumor tissues showed statistically significant (p < 0.0005) changes, compared to normal tissues, in the expression of hsa-let-7i-5p (increased by 4.2 times in stage IV), hsa-miR-126-5p (increased by 2.0; 2.1 and 2.9 times in stages II, III and IV, respectively), hsa-miR-143-3p (decreased by 3.3 times in stage IV), hsa-miR-21-5p (increased by 3.9 and 4.8 times in stages III and IV), hsa-miR-25-3p (increased by 3.2 times in stage IV), hsa-miR-26a-5p (decreased by 10.0; 5.0 and 6.7 times in stages II, III and IV, respectively) and hsa-miR-92a-3p (increased by 2.2; 5.1 and 9.5 times in stages II, III and IV, respectively). We observed changes in the expression of hsa-let-7i-5p (increased by 3.4 times), hsa-miR-143-3p (decreased by 3.4 times), hsa-miR-21-5p (increased by 3.2 times) and hsa-miR-92a-3p (increased by 4.3 times) in tumors of patients with stage IV disease, compared to stage II (p < 0.005). CTC expression of miRNAs hsa-miR-143-3p, hsa-miR-21-5p, hsa-miR-26a-5p in patients with lymph node metastases, compared to patients without metastases, was decreased by 2.5; 3.6; 5.0 times (p < 0.05) respectively, and expression of hsa-miR-92a-3p was elevated by 3.0 times (p < 0.05). In patients with liver metastases, CTC expression of hsa-miR-143-3p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-26a-5p was statistically significantly (p < 0.05) lower by 4.6; 5.5; 1.7; 5.3 times, respectively, compared to the CTC expression in patients without metastases, and expression of hsa-miR-126-5p and hsa-miR-92a-3p was higher by 2.6 and 5.0 times, respectively, compared to the CTC expression in patients without metastases (p < 0.05). CTC expression of hsa-miR-143-3p was 1.8 times lower (p < 0.05), and expression of hsa-miR-92a-3p was 1.7 times (p < 0.05) higher in patients with distant metastases, compared to patients with regional metastases. Conclusions: On the whole, the miRNA expression profile in the tumor and CTCs in CC were similar, although there were some differences. Tumor tissues in stage IV patients were characterized by overexpression of hsa-let-7i-5p, which is not typical for CTCs. The levels of the tumor suppressor hsa-miR-26a-5p were reduced in tumors of different stages to similar values, but differed in CTCs, which allows differentiation between non-metastatic CC and metastatic CRC.