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 researches have reported some component of PM2.5, promotes pulmonary injury by modifying lipid metabolism. However, there are less researches regarding the association between transcriptome-wide lipid metabolism and lung cancer. Therefore, this study using the LUAD cohort to generate the transcriptome-wide profile of lipid-related. Similar to the previous studies regarding other kinds of cancers, the fatty acid, glycerolipid, and glycerophospholipids were also the primary driven enrichment biological function. Besides, arachidonic acid metabolism, PPAR signaling pathway, insulin resistance, eicosanoids signaling, and other pathways and GO terms are also reported to find in cancer[35–37]. From the network of those biological function modules, which were connected with genes shared between modules, the lipid metabolic of LUAD was associated with nicotine, estrogen biosynthesis, melatonin, and atherosclerosis. Nicotine may promote LUAD development by regulating lipid metabolism. The interaction between estrogen biosynthesis and lipid metabolic is one of the high-risk factors of LUAD, which is consistent with the tread that lung cancer incidence is rising in women and has, in fact, more than doubled since the mid1970s. Atherosclerosis and cancer have many similarities. Patients with atherosclerotic disease are prone to repeated episodes of ischemia/reperfusion, which induces oxidative stress through the formation of oxygen free radicals. Endogenous exposure to free radicals increases the risk of cancer in individuals with atherosclerotic diseases. Besides, retinoic acid inducing RAR-beta /RXR activation to promote tumor progression should be a potential way to promote LUAD. RXR can activate FXR/RXR and LXR/RXR, and the two activations also overlap. FXR has been reported as a tumor suppressor. A possible mechanism is that FXR activates CCND1 expression and promotes cell proliferation. In order to activate the expression of its target genes, FXR is a heterodimer with retinoid X receptor alpha (RXRα). It binds to FXR response element (FXRE) after activation by a specific agonist, mainly IR-1. Besides, FXR has been recently found related to the microenvironment of immunotherapy closely. Through FXR/RXR and LXR/RXR, lipid metabolic may influence the development of LUAD by regulating the immunity system.
To find the potential interventional target of LUAD patients, 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, the tumorigenesis was regulated[43, 44]. 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 UGT1A have a better prognosis (Fig. 3). DGAT1 and LPL are lipid metabolic genes. Both of them are involved in fatty acid synthesis. HPGDS has the therapeutic potential in allergic inflammation. 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 fatty acid synthesis and insulin and the inflammation control may be the treatment of LUAD patients. Based on those six genes, a risk model was constructed. LUAD patients from two cohorts with the lower risk score had a better prognosis.