Table_2_The Comprehensive Analyses of Genomic Variations and Assessment of TMB and PD-L1 Expression in Chinese Lung Adenosquamous Carcinoma.XLSX

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.

肺腺鳞癌（lung adenosquamous carcinoma, ASC）患者预后不良且治疗选择匮乏，是当前临床面临的重大挑战。既往研究表明，肿瘤突变负荷（tumor mutational burden, TMB，即每兆碱基的突变数）可作为多种癌症类型临床试验中临床应答的预测因子，但针对TMB水平与肺腺鳞癌临床特征及预后关联的研究相对较少。本研究纳入了中国肺腺鳞癌患者，从福尔马林固定石蜡包埋（formalin-fixed paraffin-embedded）的肿瘤样本中提取DNA，进行下一代测序（next generation sequencing, NGS），并对457个癌症相关基因进行检测分析。结果显示，入组患者中共鉴定出95个携带体细胞变异的独特基因。高频突变排名前三的基因为TP53、EGFR和PIK3CA，突变率分别为62%（13例）、48%（10例）及14%（3例）。本研究发现，TMB值与病理分期（p < 0.05）及淋巴结侵犯（p < 0.05）显著相关，但TMB值与其他临床病理指标无显著相关性，包括年龄、性别、吸烟史、肿瘤大小，以及肺腺鳞癌中的TP53和EGFR突变。此外，TMB值与总生存期（overall survival, OS）显著相关（p < 0.01），但与无复发生存期（relapse-free survival, RFS）无显著关联（p = 0.23）。综上，本研究表明，高TMB的肺腺鳞癌可能与淋巴结侵犯及总生存期缩短相关，免疫治疗或可成为高TMB肺腺鳞癌患者的潜在治疗选择。