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Background <p>Despite significant advancements in the field of immunotherapy for esophageal cancer in recent years, only a minority of patients respond to these treatments, and effective predictive biomarkers remain elusive. Biomarkers such as programmed cell death 1 ligand 1 (PD-L1), tumor mutational burden (TMB), and microsatellite instability (MSI) are pivotal in guiding immune checkpoint inhibitor therapies. This study aimed to explore the correlation between the three biomarkers in patients with esophageal carcinoma.</p> Methods <p>We collected one hundred esophageal squamous cell carcinoma (ESCC) tumor samples from patients who have been undergoing radical resection of esophageal carcinoma. Each tissue sample was divided into two parts for next-generation sequencing (NGS) and immunohistochemical staining. Mutations were identified using the NGS database, and TMB was calculated. Multiplex PCR targeting five loci (NR21, NR24, NR27, BAT25, and BAT26) was used to evaluate MSI. PD-L1 expression was determined through immunohistochemical analysis.</p> Results <p>Among the 100 ESCC patients, 54% (54/100) exhibited positive PD-L1 expression, 57% (57/100) demonstrated high TMB (TMB-H), and only 1% (1/100) had high MSI (MSI-H). Within the subset of TMB-H cases, 32 showed positive PD-L1 expression, with a single case displaying high expression of all three biomarkers, and 21 cases displaying low expression of all three biomarkers. There was no statistical association between PD-L1 expression levels and TMB. Further analysis showed a significant correlation between TNM staging and PD-L1 expression levels in ESCC tissues, with higher positive rates of PD-L1 expression observed in advanced stages. Similarly, a significant relationship was observed between TMB and lymph node metastasis.</p> Conclusions <p>Based on our preliminary results, TMB and PD-L1 can serve as potential early screening clinical biomarkers and molecular targets for immune treatment in ESCC. However, there is no apparent statistical association between TMB and PD-L1 expression levels. Furthermore, PD-L1 and TMB may independently influence the efficacy of immunotherapy, highlighting the inadequacy of single-marker detection in effectively predicting treatment outcomes.</p>

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Clinicopathological characteristics and the relationship of PD-L1 status, tumor mutation burden, and microsatellite instability in patients with esophageal carcinoma

  • 期刊论文

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  • 发表日期：

    2025年3月31日

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  • Suyao Li,
  • Yongling Yu,
  • Yirong Xu,
  • Yue Zhou,
  • Junxing Huang,
  • Jinghao Jia

摘要

Background

Despite significant advancements in the field of immunotherapy for esophageal cancer in recent years, only a minority of patients respond to these treatments, and effective predictive biomarkers remain elusive. Biomarkers such as programmed cell death 1 ligand 1 (PD-L1), tumor mutational burden (TMB), and microsatellite instability (MSI) are pivotal in guiding immune checkpoint inhibitor therapies. This study aimed to explore the correlation between the three biomarkers in patients with esophageal carcinoma.

Methods

We collected one hundred esophageal squamous cell carcinoma (ESCC) tumor samples from patients who have been undergoing radical resection of esophageal carcinoma. Each tissue sample was divided into two parts for next-generation sequencing (NGS) and immunohistochemical staining. Mutations were identified using the NGS database, and TMB was calculated. Multiplex PCR targeting five loci (NR21, NR24, NR27, BAT25, and BAT26) was used to evaluate MSI. PD-L1 expression was determined through immunohistochemical analysis.

Results

Among the 100 ESCC patients, 54% (54/100) exhibited positive PD-L1 expression, 57% (57/100) demonstrated high TMB (TMB-H), and only 1% (1/100) had high MSI (MSI-H). Within the subset of TMB-H cases, 32 showed positive PD-L1 expression, with a single case displaying high expression of all three biomarkers, and 21 cases displaying low expression of all three biomarkers. There was no statistical association between PD-L1 expression levels and TMB. Further analysis showed a significant correlation between TNM staging and PD-L1 expression levels in ESCC tissues, with higher positive rates of PD-L1 expression observed in advanced stages. Similarly, a significant relationship was observed between TMB and lymph node metastasis.

Conclusions

Based on our preliminary results, TMB and PD-L1 can serve as potential early screening clinical biomarkers and molecular targets for immune treatment in ESCC. However, there is no apparent statistical association between TMB and PD-L1 expression levels. Furthermore, PD-L1 and TMB may independently influence the efficacy of immunotherapy, highlighting the inadequacy of single-marker detection in effectively predicting treatment outcomes.