Goto Taichiro, Kunimasa Kei, Hirotsu Yosuke, Nakagomi Takahiro, Yokoyama Yujiro, Higuchi Rumi, Otake Sotaro, Oyama Toshio, Amemiya Kenji, Mochizuki Hitoshi, Omata Masao
Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Yamanashi 400-8506, Japan.
Genome Analysis Center, Yamanashi Central Hospital, Yamanashi 400-8506, Japan.
Cancers (Basel). 2020 Nov 21;12(11):3472. doi: 10.3390/cancers12113472.
Findings on mutations, associated with lung cancer, have led to advancements in mutation-based precision medicine. This study aimed to comprehensively and synthetically analyze mutations in lung cancer, based on the next generation sequencing data of surgically removed lung tumors, and identify the mutation-related factors that can affect clinical outcomes. Targeted sequencing was performed on formalin-fixed paraffin-embedded surgical specimens obtained from 172 patients with lung cancer who underwent surgery in our hospital. The clinical and genomic databases of the hospital were combined to determine correlations between clinical factors and mutation profiles in lung cancer. Multivariate analyses of mutation-related factors that may affect the prognosis were also performed. Based on histology, was the driver gene in 70.0% of the cases of squamous cell carcinoma. In adenocarcinoma cases, driver mutations were detected in (26.0%), (25.0%), and epidermal growth factor receptor () (23.1%). According to multivariate analysis, the number of pathogenic mutations (≥3), presence of a mutation, and allele fraction >60 were poor prognostic mutational factors. The allele fraction tended to be high in caudally and dorsally located tumors. Moreover, -mutated lung cancers located in segments 9 and 10 were associated with significantly poorer prognosis than those located in segments 1-8. This study has identified mutation-related factors that affect the postoperative prognosis of lung cancer. To our knowledge, this is the first study to demonstrate that the mutation profile varies with the site of lung tumor, and that postoperative prognosis varies accordingly.
与肺癌相关的突变研究成果推动了基于突变的精准医学发展。本研究旨在基于手术切除的肺肿瘤的下一代测序数据,全面综合地分析肺癌中的突变情况,并确定可能影响临床结局的突变相关因素。对我院172例接受手术的肺癌患者的福尔马林固定石蜡包埋手术标本进行了靶向测序。结合医院的临床和基因组数据库,以确定肺癌临床因素与突变谱之间的相关性。还对可能影响预后的突变相关因素进行了多因素分析。在组织学方面,在70.0%的鳞状细胞癌病例中,[此处原文缺失相关基因名称]是驱动基因。在腺癌病例中,检测到[此处原文缺失相关基因名称](26.0%)、[此处原文缺失相关基因名称](25.0%)和表皮生长因子受体([此处原文缺失相关基因名称])(23.1%)的驱动突变。根据多因素分析,致病突变数量(≥3)、[此处原文缺失相关基因名称]突变的存在以及[此处原文缺失相关基因名称]等位基因分数>60是不良预后的突变因素。[此处原文缺失相关基因名称]等位基因分数在位于尾侧和背侧的肿瘤中往往较高。此外,位于第9和第10段的[此处原文缺失相关基因名称]突变型肺癌的预后明显比位于第1 - 8段的肺癌差。本研究确定了影响肺癌术后预后的突变相关因素。据我们所知,这是第一项证明[此处原文缺失相关基因名称]突变谱随肺肿瘤部位而变化且术后预后也相应不同的研究。