Liu Zhenghao, Zheng Meiguang, Lei Bingxi, Zhou Zhiwei, Huang Yutao, Li Wenpeng, Chen Qinbiao, Li Pengcheng, Deng Yuefei
Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Thoracic Oncology, Cancer Center of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ann Transl Med. 2021 Apr;9(8):694. doi: 10.21037/atm-21-1555.
Lung cancer is the most aggressive cancer, resulting in one-quarter of all cancer-related deaths, and its metastatic spread accounts for >70% of these deaths, especially metastasis to the brain. Metastasis-associated mutations are important biomarkers for metastasis prediction and outcome improvement.
In this study, we applied whole-exome sequencing (WES) to identify potential metastasis-related mutations in 12 paired lung cancer and brain metastasis samples.
We identified 1,702 single nucleotide variants (SNVs) and 6,131 mutation events among 1,220 genes. Furthermore, we identified several lung cancer metastases associated genes (, ). A mean of 3.1 driver gene mutation events per tumor with the dN/dS (non-synonymous substitution rate/synonymous substitution rate) of 2.13 indicating a significant enrichment for cancer driver gene mutations. Mutation spectrum analysis found lung-brain metastasis samples have a more similar Ti/Tv (transition/transversion) profile with brain cancer in which C to T transitions are more frequent while lung cancer has more C to A transversion. We also found the most important tumor onset and metastasis pathways, such as chronic myeloid leukemia, ErbB signaling pathway, and glioma pathway. Finally, we identified a significant survival associated mutation gene in both The Cancer Genome Atlas (TCGA) (P=0.01) and our dataset (P=0.012).
In summary, we conducted a pairwise lung-brain metastasis based exome-wide sequencing and identified some novel metastasis-related mutations which provided potential biomarkers for prognosis and targeted therapeutics.
肺癌是最具侵袭性的癌症，导致四分之一的癌症相关死亡，其转移扩散占这些死亡的70%以上，尤其是脑转移。转移相关突变是转移预测和改善预后的重要生物标志物。
在本研究中，我们应用全外显子组测序（WES）来鉴定12对肺癌和脑转移样本中潜在的转移相关突变。
我们在1220个基因中鉴定出1702个单核苷酸变异（SNV）和6131个突变事件。此外，我们还鉴定出了几个肺癌转移相关基因（，）。每个肿瘤平均有3.1个驱动基因突变事件，dN/dS（非同义替换率/同义替换率）为2.13，表明癌症驱动基因突变显著富集。突变谱分析发现，肺-脑转移样本与脑癌的Ti/Tv（转换/颠换）谱更相似，其中C到T的转换更频繁，而肺癌中C到A的颠换更多。我们还发现了最重要的肿瘤发生和转移途径，如慢性髓性白血病、表皮生长因子受体（ErbB）信号通路和胶质瘤通路。最后，我们在癌症基因组图谱（TCGA）（P=0.01）和我们的数据集中（P=0.012）都鉴定出了一个与生存显著相关的突变基因。
总之，我们基于肺-脑转移对进行了全外显子组测序，并鉴定出一些新的转移相关突变，为预后和靶向治疗提供了潜在的生物标志物。
