Abstract 14P
Background
Colorectal cancer (CRC) is a heterogeneous disease with high incidence and malignancy. Lipid metabolic reprogramming is involved in the development of CRC and may be regulated by oncogenes. This study aims to investigate the correlation between lipid metabolism and RAS/RAF status in CRC patients, and its prognostic value.
Methods
A total of 291 CRC patients were enrolled and divided into wild-type (WT) and mutant (MT) groups who underwent radical resection and RAS/RAF molecular test. SPSS 26.0 software was used to compare clinicopathologic characteristics and preoperative serum lipids and to analyze independent risk factors for gene mutation and prognosis of CRC in different groups. RAF/RAF mutation-related genes and lipid metabolism-related genes (LMRGs) were downloaded from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB). Expression and prognostic values of overlapping genes were validated in GSE39582 of the Gene Expression Omnibus (GEO) by R 4.3.1 software.
Results
KRAS mutations accounted for 43.6% of all CRC patients, followed by NRAS and BRAF, significantly associated with women, right-sided CRC, higher N stage and TNM stage (P<0.05). Women and right-sided CRC were independent predictors of KRAS mutation (P<0.05). KRAS-MT patients had higher cholesterol (CHOL) and high-density lipoprotein (HDL) than KRAS-WT patients (P<0.05). While clinicopathologic features and serum lipids didn't vary significantly across NRAS or BRAF status (P>0.05). Right-sided CRC and higher HDL were independent risk factors for DFS of KRAS-MT patients (P<0.05). Higher CHOL and HDL were independent risk factors for DFS of KRAS-WT patients and NRAS-WT patients, respectively (P<0.05). Based on the TCGA-CRC database, there are 6、3, and 34 LMRGs associated with KRAS、NRAS and BRAF mutation, respectively (AGMO, etc.; ACSL6, etc.; CYP4F8, etc., respectively) (P<0.05). As demonstrated in GSE39582, they are differentially expressed in tumors and associated with prognosis (P<0.05).
Conclusions
Both high CHOL and HDL in CRC patients correlated with KRAS mutation, and lipids have prognostic value for CRC with different RAS/ RAF status. RAS/ RAF mutations were also associated with lipid metabolism reprogramming in the microenvironment of CRC.
Legal entity responsible for the study
C. Huang.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.