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Background: Long-chain acyl-CoA synthetase-4 (ACSL4) is involved in fatty acid metabolism, and aberrant ACSL4 expression could be either tumorigenic or tumor-suppressive in different tumor types. However, the function and clinical significance of ACSL4 in lung adenocarcinoma remain elusive. Results: ACSL4 was frequently downregulated in lung adenocarcinoma when analyzing both the TCGA database and the validation samples, and the lower ACSL4 expression was correlated with a worse prognosis. Using gene set enrichment analysis, we found that high ACSL4 expression was frequently associated with the oxidative stress pathway, especially ferroptosis-related proteins. In vitro functional studies showed that knockdown of ACSL4 increased tumor survival/invasiveness and inhibited ferroptosis, while ACSL4 overexpression exhibited the opposite effects. Moreover, high-fat treatment could also inhibit erastin-induced ferroptosis by affecting ACSL4 expression. The anti-tumor effects of ferroptosis inducers and the anti-ferroptosis effects of the high-fat diet were further validated using the mouse xenograft model. Conclusions: ACSL4 plays a tumor-suppressive role in lung adenocarcinoma by suppressing tumor survival/invasiveness and promoting ferroptosis. Our study provided a theoretical reference for the application of ferroptotic inducers and dietary guidance for lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

Efficacy comparison of icotinib and pemetrexed in the treatment of lung adenocarcinoma and the effects on the prognostic survival rate of patients were investigated. A retrospective analysis was performed in 132 lung adenocarcinoma patients who were treated in the Affiliated Hospital of Weifang Medical University from July 2010 to July 2015. Among them, 69 patients were treated with icotinib (icotinib group), and 63 patients were treated with pemetrexed (pemetrexed group). In the icotinib group, 125 mg icotinib was orally administered continuously, 3 times a day, until progressive disease or intolerable adverse reactions occurred. In the pemetrexed group, 500 mg/m2 pemetrexed was intravenously dripped for a total of 4 cycles, 21 days for 1 cycle, until progressive disease or intolerable adverse reactions occurred. The efficacy, toxic and side effects, and survival rate of the two groups were evaluated. There was a statistically significant difference in toxic and side effects between the two groups of drugs after the treatment of lung adenocarcinoma (P<0.05). The median survival time of patients was 16 months in the icotinib group and 10 months in the pemetrexed group, with a statistically significant difference (P<0.05). The 1-year survival rate was higher in the icotinib group than that in the pemetrexed group (P<0.05). There was no difference in 2- and 3-year survival rates between the two groups (P>0.05). In conclusion, the clinical efficacy of icotinib is similar to that of pemetrexed in the treatment of lung adenocarcinoma, but icotinib has less adverse reactions, with better improvement in disease control. [ABSTRACT FROM AUTHOR]