J Cancer 2020; 11(14):4213-4221. doi:10.7150/jca.35014

Research Paper

High expression of folate cycle enzyme MTHFD1L correlates with poor prognosis and increased proliferation and migration in colorectal cancer

Zhongyun He1*, Xia Wang1*, Huizhong Zhang3, Baoxia Liang2, Jinling Zhang2, Zhenfeng Zhang2✉, Yi Yang1,4✉

1. Department of Pathology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR, China.
2. Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR, China.
3. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, PR, China.
4. Boba Evergrande International Hospital, Qionghai, PR, China.
*Zhongyun He and Xia Wang contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
He Z, Wang X, Zhang H, Liang B, Zhang J, Zhang Z, Yang Y. High expression of folate cycle enzyme MTHFD1L correlates with poor prognosis and increased proliferation and migration in colorectal cancer. J Cancer 2020; 11(14):4213-4221. doi:10.7150/jca.35014. Available from http://www.jcancer.org/v11p4213.htm

File import instruction

Abstract

Aims: To investigate the expression and clinical significance of methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) in colorectal cancer (CRC) and its effect on CRC cells proliferation and migration.

Methods: 59 fresh CRC tissue samples and matched normal tissues, 176 archive CRC tissue samples and 8 CRC cell lines were tested MTHFD1L by western blot and immunohistochemistry, respectively. The relationship between MTHFD1L expression, clinical significance and prognosis was analyzed by chi-square test and survival analysis. MTT assay, plate clonal formation assay and scratch assay were used to verify the effect of MTHFD1L on the proliferation and migration in CRC cell lines.

Results: The results showed that the protein level of MTHFD1L in CRC was significantly higher than that in adjacent normal tissues (p<0.01). The expression of MTHFD1L in CRC was positively correlated with the degree of tumor differentiation, TNM classification, tumor invasion, lymph node metastasis, and distant metastasis. Survival analysis showed that CRC patients with high MTHFD1L expression had a lower 5-year survival rate and the expression of MTHFD1L was an independent adverse factor for the CRC prognosis (p<0.05). Down-regulation of MTHFD1L inhibited the proliferation and migration of DLD-1 and HCT116 CRC cell lines.

Conclusion: These findings reveal that MTHFD1L is highly expressive in CRC and associated with poor prognosis, and MTHDF1L can increase colorectal cancer cell proliferation and migration. Therefore, MTHFD1L may serve as a predictor and a potential therapeutic target for CRC.

Keywords: colorectal cancer, MTHFD1L, prognosis, migration, proliferation