To comprehensively depict the genomic landscape of Chinese lung squamous cell carcinoma (LSCC) and investigate its correlation with tumor mutation burden (TMB), CD8 tumor infiltrating lymphocytes (TILs) density and PD-L1 expression.
Whole-exome sequencing were performed on tumor tissue collected from 189 patients with surgically resected LSCC. TMB was defined as total number of nonsynonymous single nucleotide and indel variants. High TMB was defined as greater than 75th percentile. CD8+ TILs and PD-L1 expression were assessed by immunohistochemistry. The cut-off point was 5% for high/low CD8+ TIL or PD-L1 +/- expression.
We found recurrent mutations (>5%) in 8 genes, including TP53, KMT2C, NFE2L2, KEAP1, CDKN2A, PTEN and FBXW7. FGFR1 and PIK3CA amplifications were found in 19% and 11% of samples. 24.9% of patients had high TMB. Baseline clinical variables were similar except for smoking status. Interestingly, FGFR1, PIK3CA or SOX2 amplification was independently associated with higher TMB (P = 0.020, P = 0.017, P = 0.029; respectively). Patients with copy number variations had significantly higher TMB than those without (P = 0.009). Positive PD-L1 and CD8+ TILs expression were identified in 24.3% and 78.8% of all cases. NFE2L2 mutation and PIK3CA amplification were associated with significantly higher PD-L1 expression (P = 0.003, P = 0.014; respectively). TP53 mutations were associated with higher CD8+ TILs expression (P = 0.008), but FGFR1 amplification was correlated with lower CD8+ TILs expression (P = 0.042). Of note, there is no association between TMB and PD-L1 expression (r = 0.052, P = 0.476), or CD8+ TILs expression (r = 0.026, P = 0.718). None of TMB, PD-L1 and CD8+ TIL expression could individually predict overall survival (OS). However, combination of TMB and PD-L1 could stratify total populations into two groups with distinct prognosis. Patients with negative PD-L1 expression and high TMB had the worst prognosis (P = 0.008).
This was the most large-scale study to comprehensively portray genomic landscape of Chinese LSCC and provides several meaningful and referential findings for the future design of clinical trials in LSCC, especially immunotherapy.
Clinical trial identification
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Has not received any funding.
All authors have declared no conflicts of interest.