Metabolic change has been widely observed in cancer cells. Among those metabolisms, lipid metabolism widely participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Some recent studies have reported some component of PM2.5 which has been reported as the risk factors of lung cancer[29-31], for the component of PM2.5 promotes pulmonary injury by modifying lipid metabolism and might develop to lung cancer. However, there are fewer researches regarding the association between lipid metabolism and lung cancer in the term of transcriptome-wide analysis. This study used a LUAD cohort to generate the transcriptome-wide profile of lipid-related that includes 217 genes. The enrichment biological pathway found in LUAD included fatty acid, glycerolipid, and glycerophospholipids were the primary driven enrichment biological function that has been reported. Besides, arachidonic acid metabolism, PPAR signaling pathway, insulin resistance, eicosanoids signaling, and other pathways were also reported in cancer[33-37].
The results indicate that LUAD-related lipid metabolism was associated with nicotine, estrogen biosynthesis, melatonin, and atherosclerosis. Similar to PM2.5, nicotine may promote LUAD development regulated by lipid disordered. The interaction between estrogen biosynthesis and lipid metabolic may be one of the high-risk factors for LUAD, which is consistent with the observation that LUAD incidence is rising in women, and the incidence rate among female was higher than that among men ; Lipid and cancer-related genes were enriched in atherosclerosis and cancer. For long-term survival LUAD patients, their health management should be involved by oncologists and cardiologists .
We constructed the network of those genes that are related to lipid and LUAD and find six hub genes. CYP2C9, which is a drug target of lung cancer, can be slowed by cytochrome P450; and the tumorigenesis was regulated[44, 45]. LUAD patients with a lower expression of CYP2C9 have a better prognosis. UGT1A variants may play only a minor role in other lung cancer risk. LUAD patients with a lower expression of UGT1A6 have a better prognosis. DGAT1 catalyzes the final step in triglyceride synthesis . LPL is a key lipolytic enzyme that plays a crucial role in the catabolism of triglycerides in TG-rich particles. Both of them are involved in triglyceride synthesis. And triglyceride was reported with HPGDS has the therapeutic potential in allergic inflammation. Serum triglyceride concentrations were reported to be involved in the pathogenesis of lung cancer. Those three genes were positively related to survival time. INS encodes insulin and plays a vital role in the regulation of carbohydrate and lipid metabolism. LUAD patients with a lower expression of INS have a better prognosis. The regulation of triglyceride synthesis, insulin, and inflammation control may be the effective intervention of LUAD patients. Based on those six genes, a risk model was constructed. LUAD patients from two cohorts with a lower risk score had a better prognosis.
Strengths and limitations
The main strength of the study is the establishment of a lipid metabolic transcriptome-wide profile of LUAD and a gene signature that significantly associated with the diagnosis and prognosis of LUAD patients in the term of lipid metabolism. Limitations include: 1) the data field information of these two cohorts is limited, which leading the covariables related to LUAD missed and brought bias; 2) the further internal mechanism of these six lipid-related genes cannot be illuminated in this study. A well-designed experiment based on our results was required in further research.