Tumor Mutational Burden and PD-L1 Expression in Non-Small-Cell Lung Cancer (NSCLC) in Southwestern China

Abstract

Yuhui Ma,1,* Quan Li,2,* Yaxi Du,2,* Wanlin Chen,1 Guangqiang Zhao,1 Xing Liu,2 Lianhua Ye,1 Hongsheng Li,3 Xiaoxiong Wang,3 Junxi Liu,3 Zhenghai Shen,4 Luyao Ma,2 Yongchun Zhou4 1Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming 650118, People’s Republic of China; 2Key Laboratory of Lung Cancer Research of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People’s Republic of China; 3International Joint Laboratory on High Altitude Regional Cancer of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People’s Republic of China; 4Yunnan Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongchun ZhouYunnan Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People’s Republic of ChinaTel/ Fax [phone]Email [email protected]: 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.Patients and Methods: 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.Results: 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, p = 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, p = 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, p < 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, p < 0.01).Conclusion: 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.Keywords: non-small-cell lung cancer, TMB, programmed death ligand-1 expression, next-generation sequencing

Keywords

• non-small-cell lung cancer
• tmb
• programmed death ligand-1 expression
• next-generation sequencing