Genetic variants in primary cilia-related genes associated with the prognosis of first-line chemotherapy in colorectal cancer.

ABSTRACT

BACKGROUND: Primary cilia are antenna-like organelles that conduct physical and chemical signals, which affect cell proliferation, migration, and differentiation. Some researchers have reported the correlation between primary cilia-related genes and prognosis of colorectal cancer (CRC). METHODS: The association between single nucleotide polymorphisms (SNPs) of primary cilia-related genes and outcome after the first-line chemotherapy was explored by the Cox regression model. Expression qualitative trait locus (eQTL) analysis was performed to explore the impact of SNPs on gene expression. Tumor Immune Estimation Resource and TISIDB databases were used for investigating the relevance between ODF2L and tumor infiltration immune cells and immunomodulators. RESULTS: We identified that rs4288473 C allele of ODF2L had poor progression-free survival (PFS) and overall survival (OS) of CRC patients in the additive model (adjusted HRPFS = 1.39, 95% CI = 1.14-1.70, p = 1.36 × 10-3 , and adjusted HROS = 1.31, 95% CI = 1.03-1.65, p = 2.62 × 10-2 ). The stratified analysis indicated that rs4288573 CC/CT genotype was involved with poor prognosis in the irinotecan-treated subgroup (PPFS = 1.03 × 10-2 , POS = 3.29 × 10-3 ). Besides, ODF2L mRNA expression level was notably up-regrated in CRC tissues. The C allele of rs4288573 was notably related to higher ODF2L mRNA expression levels based on eQTL analysis. Functionally, knockdown of ODF2L inhibited cell proliferation and decrease the chemoresistance of HCT-116 and DLD-1 cells to irinotecan. CONCLUSION: Our study indicates that rs4288573 in ODF2L is a potential predictor of the chemotherapy prognosis of CRC.