The Comprehensive Analyses of Genomic Variations and Assessment of TMB and PD-L1 Expression in Chinese Lung Adenosquamous Carcinoma.
The Comprehensive Analyses of Genomic Variations and Assessment of TMB and PD-L1 Expression in Chinese Lung Adenosquamous Carcinoma.
复制标题
中国肺腺鳞癌基因组变异综合分析及TMB和PD-L1表达评估
DOI：
10.3389/fgene.2020.609405
复制
发表时间：
2020
影响因子：
3.7
通讯作者：
Ye X
中科院分区：
文献类型：
--
作者：
Cheng Y;Zhang Y;Yuan Y;Wang J;Liu K;Yu B;Xie L;Ou-Yang C;Wu L;Ye X
肺腺鳞癌（ASC）预后差、治疗选择少是目前临床面临的挑战。以往的研究报道，肿瘤突变负荷（TMB，每兆碱基的突变数）是多种癌症类型试验中临床反应的预测因子，而很少有研究评估TMB水平与肺ASC的临床特征和结局之间的关系。在此，本研究招募了患有肺ASC的中国患者。从福尔马林固定的石蜡包埋的肿瘤样品中提取DNA并进行下一代测序（NGS），并评估457个癌症相关基因。结果表明，在入选的患者中鉴定出95个具有体细胞变异的独特基因。突变频率居前3位的基因依次为TP53、EGFR、PIK3CA，突变率分别为62%（13例）、48%（10例）和14%（3例）。TMB值与肿瘤病理分期（p < 0.05）及淋巴结转移（p < 0.05）相关。TMB值与年龄、性别、吸烟史、肿瘤大小、TP53和EGFR突变等临床病理指标无明显相关性。此外，TMB值与总生存率相关（p < 0.01），但与无复发生存率无关（p = 0.23）。本研究提示，肺ASC伴高TMB可能与淋巴结浸润和总生存期短有关。免疫治疗可能是高TMB的肺ASC患者的一种有前途的治疗选择。
The poor prognosis and fewer treatment option is a current clinical challenge for patients with lung adenosquamous carcinoma (ASC). The previous studies reported that tumor mutational burden (TMB, numbers of mutation per Megabase) is a predictor of clinical response in trials of multiple cancer types, while fewer studies assessed the relationship between TMB level and clinical features and outcomes of lung ASC. Herein, the present study enrolled Chinese patients with lung ASC. DNA was extracted from formalin-fixed paraffin-embedded tumor samples and subjected to next generation sequencing (NGS), and the 457 cancer related genes were evaluated. The results demonstrated that 95 unique genes with somatic variations were identified in the enrolled patients. The top three of high frequency gene mutations were TP53, EGFR, PIK3CA with rates of 62% (13 cases), 48% (10 cases), and 14% (3 cases), respectively. We identified TMB value was significantly correlated with pathological stages (p < 0.05) and invasion of lymph node (p < 0.05). However, TMB value was not significantly correlated to other clinicopathologic indexes, for examples, age, sex, smoking history, tumor size, as well as TP53 and EGFR mutations in lung ASC. Moreover, TMB value was associated with the overall survival (p < 0.01), but not with the relapse-free survival (p = 0.23). In conclusion, this study indicated that lung ASC with high TMB might be associated with the invasion of lymph node and short overall survival. Immunotherapy might be a promising treatment option for lung ASC patients with high TMB.