J Cancer 2020; 11(22):6507-6515. doi:10.7150/jca.44580 This issue
1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
2. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
3. Department of Oncology, Jiangyin People's Hospital, Wuxi, China.
4. Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
5. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
*These authors contributed equally to this work.
Background: The association between genetic variants in the folic acid metabolic pathway genes and survival, as well as the responses to chemotherapy of metastatic colorectal cancer (mCRC) patients has not been reported.
Methods: The association between genetic variants in the folic acid metabolic pathway genes and progression-free survival (PFS) and overall survival (OS) of mCRC patients were analyzed using Cox regression model. The false discovery rate (FDR) correction method was conducted. The logistic regression model was used to explore the effects of the interested genetic variants on disease control rate (DCR). The Cancer Genome Atlas (TCGA) database was applied to compare gene expression differences.
Results: We found that rs3786362 G allele of thymidylate synthase (TYMS) gene was significantly associated with PFS (P = 1.10 × 10-2), OS (P = 2.50 × 10-2) and DCR (P = 5.00 × 10-3). The expression of TYMS was overexpressed in CRC tissues compared with adjacent normal tissues. Furthermore, TYMS expression level decreased with respect to younger age and advanced tumor stage.
Conclusion: Genetic variants in the folic acid metabolic pathway genes might serve as potential prognostic biomarkers for mCRC patients.
Keywords: genetic variants, folic acid, colorectal cancer, chemotherapy