Ma Yuhui, Li Quan, Du Yaxi, Chen Wanlin, Zhao Guangqiang, Liu Xing, Ye Lianhua, Li Hongsheng, Wang Xiaoxiong, Liu Junxi, Shen Zhenghai, Ma Luyao, Zhou Yongchun
Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming 650118, People's Republic of China.
Key Laboratory of Lung Cancer Research of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People's Republic of China.
Onco Targets Ther. 2020 Jun 8;13:5191-5198. doi: 10.2147/OTT.S255947. eCollection 2020.
To explore the impact between the tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression on NSCLC in the Yunnan region of southwestern China.
Seventy-one NSCLC specimens that were pathologically confirmed were collected at first. The TMB and driver genetic alterations were evaluated accordingly by next-generation sequencing (NGS). Afterwards, clinical parameters and tumor PD-L1 expressions were collected. Finally, the relationship between TMB, PD-L1 expression and clinical outcome was evaluated.
The median TMB was 5 (0.6-49) mutations/Mb by our NGS panel and the majority of patients (63/71, 88.7%) did not receive immunotherapy. The progression-free survival (PFS) was longer in TMB-low patients versus TMB-high ones (median 18.0 vs. 9.0 months, hazard ratio = 0.34, 95% confidence interval 0.14 to 0.84, = 0.02) and the cut-off value was 10 mutations/Mb. The overall survival (OS) was longer in TMB-low patients vs. TMB-high ones (median 21.0 vs. 10.0 months, HR = 0.32, 95% CI 0.12 to 0.82, = 0.02). Notably, our study also found that, excluding the eight patients with immunotherapy, the PFS was longer in patients with TMB-low vs. TMB-high (median 19.0 vs. 8.0 months, HR = 0.11, 95% CI 0.03 to 0.39, < 0.01) and the OS was longer in TMB-low patients vs. TMB-high (median 21.0 vs 10.0 months, HR = 0.12, 95% CI 0.03 to 0.42, < 0.01).
TMB was a valid and independent prognostic biomarker for NSCLC patients' clinical outcome and comprehensive screening of TMB based on NGS is recommended for individualized treatment strategies in Yunnan population.
探讨中国西南部云南地区非小细胞肺癌（NSCLC）中肿瘤突变负荷（TMB）与程序性死亡配体-1（PD-L1）表达之间的影响。
首先收集71例经病理确诊的NSCLC标本。通过下一代测序（NGS）相应地评估TMB和驱动基因改变。之后，收集临床参数和肿瘤PD-L1表达情况。最后，评估TMB、PD-L1表达与临床结局之间的关系。
通过我们的NGS检测板，TMB中位数为5（0.6 - 49）个突变/Mb，大多数患者（63/71，88.7%）未接受免疫治疗。TMB低的患者无进展生存期（PFS）长于TMB高的患者（中位数18.0个月对9.0个月，风险比 = 0.34，95%置信区间0.14至0.84，P = 0.02），临界值为10个突变/Mb。TMB低的患者总生存期（OS）长于TMB高的患者（中位数21.0个月对10.0个月，HR = 0.32，95% CI 0.12至0.82，P = 0.02）。值得注意的是，我们的研究还发现，排除8例接受免疫治疗的患者后，TMB低的患者PFS长于TMB高的患者（中位数19.0个月对8.0个月，HR = 0.11，95% CI 0.03至0.39，P < 0.01），TMB低的患者OS长于TMB高的患者（中位数21.0个月对10.0个月，HR = 0.12，95% CI 0.03至0.42，P < 0.01）。
TMB是NSCLC患者临床结局的有效且独立的预后生物标志物，建议对云南人群基于NGS进行TMB综合筛查以制定个体化治疗策略。
