High mutations in fatty acid metabolism contribute to a better prognosis of small-cell lung cancer patients treated with chemotherapy.
High mutations in fatty acid metabolism contribute to a better prognosis of small-cell lung cancer patients treated with chemotherapy.
复制标题
脂肪酸代谢的高突变有助于接受化疗的小细胞肺癌患者更好的预后
DOI：
10.1002/cam4.4290
复制
发表时间：
2021-11
期刊：
影响因子：
4
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Lyu Q;Zhu W;Wei T;Ding W;Cao M;Wang Q;Guo L;Luo P;Zhang J
大多数小细胞肺癌（SCLC）患者在治疗的早期阶段表现出良好的反应，但超过90%的患者会产生耐药性。因此，迫切需要生物标志物来识别可以从系统治疗中获益的患者。我们前瞻性地从当地医院招募了52例治疗前的广泛期SCLC患者，以确定与患者预后相关的突变，并在已发表的Jiang队列和乔治队列中进行了验证。我们发现高突变的患者在当地医院队列中，脂肪酸（FA）代谢途径中的突变（mut‐high）患者的无进展生存期（PFS）较长（HR = 0.446，95% CI，0.207-0.959，p = 0.0387）和总生存期（OS）较长（HR = 0.549，95% CI，0.314-0.960，p = 0.0351）。多变量分析表明，在两个队列中，Mut-high状态是一个独立的预后因素。乔治的队列验证了mut-高状态与较mut-低状态更长的OS相关（HR = 0.730，95% CI 0.440-1.220，p = 0.2277）。可能的机制如下：突变型FA合成酶（FAT 3）在mut‐high组中的频率高于mut‐low组，并且与细胞周期、DNA修复和氧化磷酸化相关的通路在mut‐high组中富集。FA代谢途径突变较多的患者中，接受化疗的SCLC患者的预后更好，其潜在机制可以在基因组和转录组水平上找到。我们前瞻性地招募了52名来自当地医院的广泛期SCLC患者，以确定与患者预后相关的突变。我们发现，在当地医院队列和Jiang队列中，脂肪酸（FA）代谢途径中具有高突变（mut‐high）的患者比具有低突变（mut‐low）的患者预后更好。然后在乔治的队列中验证了mut‐high状态与mut‐low状态相比更长的OS相关。最后，从基因组和转录组水平探讨了其可能的机制。
The majority of patients with small‐cell lung cancer (SCLC) show a good response in the early stages of treatment, but more than 90% of patients will develop drug resistance. Therefore, biomarkers are urgently needed to identify patients who can benefit from systemic treatment. We prospectively enrolled 52 extensive‐stage SCLC patients before treatment from a local hospital to identify mutations related to patient prognosis, and verified them in the published Jiang's cohort and George's cohort. We found that patients with high mutations (mut‐high) in the fatty acid (FA) metabolism pathway had a longer progression‐free survival (PFS) in the local hospital cohort (HR = 0.446, 95% CI, 0.207–0.959, p = 0.0387) and a longer overall survival (OS) in Jiang's cohort (HR = 0.549, 95% CI, 0.314–0.960, p = 0.0351) than patients with low mutations (mut‐low). Multivariate analysis suggested that mut‐high status was an independent prognostic factor in both cohorts. George's cohort verified that mut‐high status was associated with a longer OS than mut‐low status (HR = 0.730, 95% CI 0.440–1.220, p = 0.2277). The possible mechanisms were as follows: the frequency of mutated FA synthase (FASN) in the mut‐high group was greater than that in the mut‐low group, and pathways related to the cell cycle, DNA repair, and oxidative phosphorylation were enriched in the mut‐high group. The prognosis of SCLC patients treated with chemotherapy was better among patients with more mutations in the FA metabolism pathway, and the underlying mechanisms could be found at the genome and transcriptome levels. We prospectively enrolled 52 extensive‐stage SCLC patients before treatment from local hospital to identify mutations related to patient prognosis. We found that the patients with high mutations (mut‐high) in the fatty acid (FA) metabolism pathway had better prognosis in the local hospital cohort and the Jiang's cohort than patients with low mutations (mut‐low). Then it was verified in George's cohort that mut‐high status was associated with a longer OS than mut‐low status. Finally, the possible mechanisms were explored from the genome and transcriptome levels.
登录
查看更多内容
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
158.5
作者：
Druker, Brian J.;Guilhot, Francois;Larson, Richard A.
通讯作者：
Larson, Richard A.
DOI：
10.1158/1078-0432.ccr-20-2925
发表时间：
2021-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Awasthi S;Berglund A;Abraham-Miranda J;Rounbehler RJ;Kensler K;Serna A;Vidal A;You S;Freeman MR;Davicioni E;Liu Y;Karnes RJ;Klein EA;Den RB;Trock BJ;Campbell JD;Einstein DJ;Gupta R;Balk S;Lal P;Park JY;Cleveland JL;Rebbeck TR;Freedland SJ;Yamoah K
通讯作者：
Yamoah K
DOI：
10.1016/j.jtho.2020.11.006
发表时间：
2021-03
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Owonikoko TK;Dwivedi B;Chen Z;Zhang C;Barwick B;Ernani V;Zhang G;Gilbert-Ross M;Carlisle J;Khuri FR;Curran WJ;Ivanov AA;Fu H;Lonial S;Ramalingam SS;Sun SY;Waller EK;Sica GL
通讯作者：
Sica GL
影响因子：
45.3
作者：
Chute, JP;Chen, T;Johnson, BE
通讯作者：
Johnson, BE