Scholarlink

Background <p>This study sought to identify new biomarkers by examining genomic profiling and PD-L1 expression. While the PD-L1 and tumor mutational burden (TMB) are currently the main clinically available biomarkers for predicting immunotherapy response in non-small-cell lung cancer (NSCLC), the factors that affect PD-L1 expression remain unclear.</p> Materials and methods <p>This retrospective study included tumor and blood samples from 2750 Chinese patients with NSCLC who had successful PD-L1 assessments and targeted next-generation sequencing. Clinicopathological characteristics and genomics profile were analyzed. TMB was categorized as high (TMB-H) if there were ≥ 10 mutations per megabase. PD-L1 expression was classified into three groups: PD-L1-negative, PD-L1-low, and PD-L1-high. In addition, genomic data, and immune checkpoint inhibitor (ICI) outcomes for 197 NSCLC patients were obtained from the MSK2020 cohort.</p> Results <p>This study included a total of 2750 NSCLC cases. Tumors with high PD-L1 expression were more commonly observed in males and exhibited a higher median TMB. Significant differences in gene mutation frequencies were observed among the different PD-L1 expression groups. Significant differences in mutation frequencies were observed in PD-L1 expression subgroups for the EGFR, TP53, LRP1B, KRAS, SPTA1, and PTPRD genes. Notably, TP53 and KRAS alterations were significantly enriched in PD-L1-high subgroup, while EGFR mutations were associated with PD-L1 negativity. Patients in the PD-L1-high group showed notably improved progression-free survival (PFS) and overall survival (OS) compared to those in the PD-L1-low and negative groups. Further analysis of the combined impact of PD-L1 expression and TMB revealed that the PD-L1-negative/TMB-low subgroup had significantly shorter PFS and OS compared to the other subgroups. This indicates that a composite biomarker combining PD-L1 expression and TMB provides superior predictive value for favorable ICI outcomes.</p> Conclusions <p>This study indicates that PD-L1 expression levels are significantly associated with specific genomic alterations and clinical outcomes in patients with NSCLC. Particularly in evaluating the efficacy of ICI therapy, the combined biomarker of PD-L1 and TMB shows important clinical application value.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genomic alteration correlates with programmed cell death ligand 1 (PD-L1) expression in 2750 Chinese non-small-cell lung cancer patients

  • 期刊论文

  • 发表日期：

    2025年6月28日

查看全文
  • Xiaohong Duan,
  • Dawei Sun,
  • Siyao Liu,
  • Junyan Su,
  • Jiali Zhang,
  • Mengyuan Liu,
  • Ning Li,
  • Ou Qiao,
  • Zichuan Liu,
  • Yanhua Gong

摘要

Background

This study sought to identify new biomarkers by examining genomic profiling and PD-L1 expression. While the PD-L1 and tumor mutational burden (TMB) are currently the main clinically available biomarkers for predicting immunotherapy response in non-small-cell lung cancer (NSCLC), the factors that affect PD-L1 expression remain unclear.

Materials and methods

This retrospective study included tumor and blood samples from 2750 Chinese patients with NSCLC who had successful PD-L1 assessments and targeted next-generation sequencing. Clinicopathological characteristics and genomics profile were analyzed. TMB was categorized as high (TMB-H) if there were ≥ 10 mutations per megabase. PD-L1 expression was classified into three groups: PD-L1-negative, PD-L1-low, and PD-L1-high. In addition, genomic data, and immune checkpoint inhibitor (ICI) outcomes for 197 NSCLC patients were obtained from the MSK2020 cohort.

Results

This study included a total of 2750 NSCLC cases. Tumors with high PD-L1 expression were more commonly observed in males and exhibited a higher median TMB. Significant differences in gene mutation frequencies were observed among the different PD-L1 expression groups. Significant differences in mutation frequencies were observed in PD-L1 expression subgroups for the EGFR, TP53, LRP1B, KRAS, SPTA1, and PTPRD genes. Notably, TP53 and KRAS alterations were significantly enriched in PD-L1-high subgroup, while EGFR mutations were associated with PD-L1 negativity. Patients in the PD-L1-high group showed notably improved progression-free survival (PFS) and overall survival (OS) compared to those in the PD-L1-low and negative groups. Further analysis of the combined impact of PD-L1 expression and TMB revealed that the PD-L1-negative/TMB-low subgroup had significantly shorter PFS and OS compared to the other subgroups. This indicates that a composite biomarker combining PD-L1 expression and TMB provides superior predictive value for favorable ICI outcomes.

Conclusions

This study indicates that PD-L1 expression levels are significantly associated with specific genomic alterations and clinical outcomes in patients with NSCLC. Particularly in evaluating the efficacy of ICI therapy, the combined biomarker of PD-L1 and TMB shows important clinical application value.