Ｅｘｐｒｅｓｓｉｏｎ ｏｆ ｓｅｒｕｍ ｍｉＲ⁃２１⁃５ｐ， ｍｉＲ⁃３７７⁃３ｐ ｉｎ ｐａｔｉｅｎｔｓ ｗｉｔｈ ｃｏｌｏｒｅｃｔａｌ ｃａｎｃｅｒ ａｎｄ ｔｈｅ ｒｅｌａｔｉｏｎｓｈｉｐ ｂｅｔｗｅｅｎ Ｗｎｔ ／ β⁃
ｃａｔｅｎｉｎ ｓｉｇｎａｌ ｐａｔｈｗａｙ ａｎｄ ｐｒｏｇｎｏｓｉｓ Ｈｕ Ｌｉｈｏｎｇ， Ｐａｎ Ｘｕｅｆｅｎｇ， Ｇｕａｎ Ｊｉａｈｅｎｇ， Ｚｈａｎｇ Ｑｉａｎ， Ｚｈｅｎｇ Ｇｕｏｂａｏ． Ｄｅｐａｒｔｍｅｎｔ
ｏｆ Ｏｎｃｏｌｏｇｙ， Ｔｈｅ ９８９ Ｈｏｓｐｉｔａｌ ｏｆ ｔｈｅ Ｊｏｉｎｔ Ｓｕｐｐｏｒｔ Ｆｏｒｃｅ ｏｆ ｔｈｅ Ｃｈｉｎｅｓｅ Ｐｅｏｐｌｅ＇ｓ Ｌｉｂｅｒａｔｉｏｎ Ａｒｍｙ， Ｈｅｎａｎ Ｐｒｏｖｉｎｃｅ， Ｌｕｏｙａｎｇ
４７１０３１，Ｃｈｉｎａ
Ｃｏｒｒｅｓｐｏｎｄｉｎｇ ａｕｔｈｏｒ： Ｚｈｅｎｇ Ｇｕｏｂａｏ， Ｅ⁃ｍａｉｌ： ｚｈｅｎｇｇｕｏｂａｏ１２３＠ １２６． ｃｏｍ
Ｆｕｎｄｉｎｇ ｐｒｏｇｒａｍ： Ｈｅｎａｎ Ｍｅｄｉｃａｌ Ｓｃｉｅｎｃｅ ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｒｅｓｅａｒｃｈ Ｐｒｏｇｒａｍ（ ＬＨＧＪ２０２１０６１３）

Abstract：

Objective To study the expression of serum microRNA(miR)-21-5p, miR-377-3p in patients with colorectal cancer(CRC) and their correlation with Wnt/β-catenin pathway and prognosis. Methods From January 2017 to January 2018, 92 patients with CRC admitted to the Oncology Department of the 989th Hospital of the Joint Service Support Force of the Chinese People's Liberation Army were selected as the CRC group, and 60 patients undergoing physical examination in the hospital during the same period were selected as the health control group. Detection of serum miR-21-5p, miR-377-3p expression and Wnt/β-Catenin pathway indicators Wnt3a β-MRNA expression levels of catenin, c-myc, and cyclin D1. Pearson correlation analysis miR-21-5p, miR-377-3p, and Wnt3a β-Correlation between expression of Catenin, c-myc, and Cyclin D1 mRNA. To compare the differences in the expression of miR-21-5p and miR-377-3p in serum of CRC patients with different clinical and pathological characteristics. Kaplan Meier curve and Logrank test were used to analyze the difference in prognosis of patients with CRC with different serum miR-21-5p and miR-377-3p expressions. Multivariate Cox regression analysis was used to analyze the prognostic factors of patients with CRC. Results Compared with the healthy control group, the expression levels of serum miR-21-5p, Wnt3a, β-catenin, c-myc, and Cyclin D1 mRNA were increased, while the expression level of miR-377-3p was decreased in the CRC group(t/P=29.202/<0.001, 52.006/<0.001, 45.973/<0.001, 39.196/<0.001, 23.119/<0.001, 38.120/<0.001). Serum miR-21-5p was positively correlated with the expression of Wnt3a, β-catenin, c-myc, and Cyclin D1 mRNA(r/P=0.404/<0.001, 0.410/0.002, 0.529/<0.001, 0.378/<0.001), while miR-377-3p was negatively correlated with the expression of Wnt3a, β-catenin, c-myc, and Cyclin D1 mRNA(r/P=-0.347/0.007,-0.408/<0.001,-0.450/<0.001,-0.419/<0.001). The serum miR-21-5p expression level in CRC patients with TNM stage III-IV and lymph node metastasis was significantly higher than that in patients with TNM stage I-II and without lymph node metastasis, while the serum miR-377-3p expression level was significantly lower(t/P=19.741/<0.001, 18.534/<0.001, 11.799/<0.001, 17.639/<0.001). The 3-year survival rate of patients with high serum miR-21-5p expression was lower than that of patients with low expression(χ²/P=17.700/<0.001), while the 3-year survival rate of patients with low miR-377-3p expression was lower than that of patients with high expression(χ²/P=21.380/<0.001). Multivariate Cox regression analysis showed that tumor TNM stage III-IV, lymph node metastasis, and elevated miR-21-5p were independent risk factors for CRC prognosis [OR(95%CI)=1.875(1.322-2.662), 1.662(1.163-2.374), 1.847(1.366-2.500)], while elevated miR-377-3p was an independent protective factor [OR(95%CI)=0.518(0.363-0.739)].Conclusion In patients with CRC, the expression of miR-21-5p in serum increases and the expression of miR-377-3p decreases, both can be regulated by Wnt/β-Catenin pathway promotes tumor progression in CRC and can be used as a tumor marker to assist in evaluating the prognosis of patients with CRC.

Colorectal cancer;                    miR-21-5p;                    miR-377-3p;                    Wnt/β-catenin pathway;                    Prognosis;