Background:Lung cancer is one of the leading causes of cancer-related mortality. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) differ in aggressiveness, proliferation speed, metastasis propensity, and prognosis. Since tumor cells notably change lipid metabolism, especially phospholipids and fatty acids (FA), this study aimed to identify FA alterations in lung cancer tissues.Methods: Our study included patients with newly diagnosed, histologically confirmed SCLC (n= 27) and NSCLC (n= 37). Samples were collected from both malignant and healthy tissues from each patient, providing they were within subject design.Results: In both NSCLC and SCLC tumor tissues, FA contents were shifted toward pro-inflammatory profiles, with increased levels of some individual n-6 polyunsaturated FA (PUFA), particularly arachidonic acid, and elevated activity of Δ6 desaturase. Compared to healthy counterparts, lower levels of alpha-linolenic acid (18:3n-3) and total saturated FA (SFA) were found in NSCLC, while decreased levels of linoleic acid (18:2n-6) and all individual n-3 FA were found in SCLC tissue in comparison to the healthy tissue control. When mutually compared, SCLC tissue had higher levels of total SFA, especially stearic acid, while higher levels of linoleic acid, total PUFA, and n-3 and n-6 PUFA were detected in NSCLC. Estimated activities of Δ6 desaturase and elongase were higher in SCLC than in NSCLC.Conclusions: Our findings indicate a notable impairment of lipid metabolism in two types of lung cancer tissues. These type-specific alterations may be associated with differences in their progression and also point out different therapeutic targets.
背景:肺癌是癌症相关死亡的主要原因之一。非小细胞肺癌(NSCLC)与小细胞肺癌(SCLC)在侵袭性、增殖速度、转移倾向及预后方面存在差异。鉴于肿瘤细胞会显著改变脂质代谢,特别是磷脂和脂肪酸(FA),本研究旨在识别肺癌组织中的脂肪酸变化。 方法:本研究纳入新诊断且经组织学确诊的SCLC患者(n=27)和NSCLC患者(n=37)。从每位患者的恶性组织和健康组织中采集样本,采用自身对照设计。 结果:在NSCLC和SCLC肿瘤组织中,脂肪酸含量均向促炎性谱系偏移,表现为部分n-6多不饱和脂肪酸(PUFA)水平升高(尤其是花生四烯酸),以及Δ6去饱和酶活性增强。与健康组织相比,NSCLC组织中α-亚麻酸(18:3n-3)和总饱和脂肪酸(SFA)水平较低;而SCLC组织中亚油酸(18:2n-6)及所有n-3脂肪酸水平均低于健康对照组织。两类肿瘤组织相互比较显示:SCLC组织的总SFA(特别是硬脂酸)水平更高,而NSCLC组织的亚油酸、总PUFA、n-3与n-6 PUFA水平更高。SCLC组织中Δ6去饱和酶和延长酶的估算活性高于NSCLC组织。 结论:我们的研究结果表明两种类型肺癌组织均存在显著的脂质代谢紊乱。这些类型特异性的改变可能与其进展差异相关,同时也提示了不同的治疗靶点。
Metabolic Reprogramming of Phospholipid Fatty Acids as a Signature of Lung Cancer Type