Whole exome analysis reveals the genomic profiling related to chemo-resistance in Chinese population with limited-disease small cell lung cancer.
Whole exome analysis reveals the genomic profiling related to chemo-resistance in Chinese population with limited-disease small cell lung cancer.
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DOI：
10.1002/cam4.4950
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发表时间：
2023-01
期刊：
影响因子：
4
通讯作者：
Wang, Lvhua
中科院分区：
文献类型：
--
作者：
Yu, Jiangyong;Zhao, Shuangtao;Su, Zhe;Song, Chengli;Wu, Lihong;Wang, Jingbo;Bi, Nan;Wang, Lvhua
小细胞肺癌（SCLC）的化疗耐药机制尚不清楚。本研究旨在通过全外显子测序（WES），探究小细胞肺癌新辅助化疗（NAC）后残留肿瘤的耐药相关基因组图谱。
本研究对416例接受手术治疗的局限性疾病（LD）小细胞肺癌患者进行回顾性分析，其中40例患者接受了新辅助化疗。随后，我们选取了29例接受新辅助化疗（n = 19）和未接受过化疗（CTN，n = 10）的患者，对福尔马林固定石蜡包埋的肿瘤及配对癌旁样本进行WES测序。
总体而言，新辅助化疗组和未化疗组的单核苷酸变异和突变率相似。新辅助化疗组与未化疗组之间，以及部分缓解（PR）、病情稳定（SD）和疾病进展的患者之间，突变特征存在显著差异。与未化疗组相比，新辅助化疗组的拷贝数变异缺失更多。TP53和RB1失活在新辅助化疗组和未化疗组中都是最为显著的事件。RB1无义突变在新辅助化疗组中反复出现（9/19对0/9，47.4%对0%），且患者生存情况较好，而移码缺失在未化疗组中更为常见（3/9对3/19，33.3%对15.8%）。综合功能富集分析显示，在新辅助化疗组中，频繁突变的基因参与细胞周期、代谢重编程和致癌信号通路，如BTG2通路、衰老中的糖酵解以及P53通路。共有27个基因在新辅助化疗组中频繁突变，可能在耐药中发挥积极作用。包括BRINP3、MYH6、ST18和PCHD15在内的多个与预后相关的基因，在部分缓解和病情稳定组中频繁发生突变。
新辅助治疗后的残留肿瘤呈现出不同的突变特征谱。包括RB1无义突变、BRINP3、MYH6、ST18和PCHD15在内的多个基因在残留肿瘤中频繁突变，这可能参与了局限性疾病小细胞肺癌患者的化疗耐药并影响其预后。
小细胞肺癌化疗耐药相关的基因组改变 。
The mechanism of chemo‐resistance in small cell lung cancer (SCLC) is unclear. This study aims to explore the resistance‐related genomic profiles of residual tumors after neo‐adjuvant chemotherapy (NAC) in SCLC through the whole‐exome sequencing (WES). A total of 416 limited diseases (LD) SCLC patients underwent surgery were retrospectively analyzed, of which 40 patients received NAC. Then we selected 29 patients undergoing NAC (n = 19) and chemotherapy naïve (CTN, n = 10) to perform WES sequence with formalin‐fixed paraffin‐embedded samples including tumor and paired para‐tumor. In total, single nucleotide variation and mutation rate were similar between NAC and CTN groups. The mutation signatures were significantly discrepant between NAC and CTN groups, as well as among patients with partial response (PR), stable disease (SD), and progressive disease. There were more copy number variation deletions in NAC group compared with CTN group. The inactivation of TP53 and RB1 were the most significantly events in both NAC and CTN groups. RB1 nonsense mutations were recurrent in NAC group (9/19 vs. 0/9, 47.4% vs. 0%) with favorable survival, while the frame‐shift deletions were frequent in CTN group (3/9 vs. 3/19, 33.3% vs.15.8%). Integrated function enrichment revealed that the frequently mutant genes were involved in cell cycle, metabolic reprogramming, and oncogenic signaling pathways in NAC group, such as BTG2 pathway, glycolysis in senescence and P53 pathway. A total of 27 genes presented frequently mutant in NAC group and might played a positive role in drug resistance. Multiple genes including BRINP3, MYH6, ST18, and PCHD15, which were associated with prognosis, occurred mutant frequently in PR and SD groups. Residual tumors after neo‐adjuvant therapy exhibited different mutation signature spectrum. Multiple genes including RB1 nonsense mutations, BRINP3, MYH6, ST18, and PCHD15 were with frequent mutation in residual tumors, which might participate chemo‐resistance and influenced the prognosis in patients with limited disease SCLC. Genomic alterations related to chemo‐resistance in small cell lung cancer.
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影响因子：
1.6
作者：
Lee YR;Kim G;Lee HW;Tak WY;Park SY;Jang SY;Kweon YO;Park JG;Han YS;Chun JM;Han JR;Hur K
通讯作者：
Hur K
DOI：
10.1016/j.matbio.2018.06.002
发表时间：
2018-10
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Mead TJ;Apte SS
通讯作者：
Apte SS
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
DOI：
10.1200/jco.20.01055
发表时间：
2021-02-20
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Liu SV;Reck M;Mansfield AS;Mok T;Scherpereel A;Reinmuth N;Garassino MC;De Castro Carpeno J;Califano R;Nishio M;Orlandi F;Alatorre-Alexander J;Leal T;Cheng Y;Lee JS;Lam S;McCleland M;Deng Y;Phan S;Horn L
通讯作者：
Horn L