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Updated: Mar 21, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Genetic alteration profiling of patients with resected squamous cell lung carcinomas
Dan Tao1, Xiaohong Han1, Ningning Zhang1
1Department of Medical Oncology, National Cancer Center/Cancer Hospital, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Abstract:
In this study, we analyzed the genetic profiles of squamous cell lung carcinoma (SqCLC) to identify potential therapeutic targets. Approximately 2,800 COSMIC mutations from 50 genes were determined by next-generation sequencing. Amplification/deletion of SOX2, CDKN2A, PTEN, FGFR1, EGFR, CCND1, HER2 and PDGFRA were detected by FISH and expression of VEGFR2, PD-L1 and PTEN were examined by IHC. One hundred and fifty-seven samples of SqCLC were collected. Somatic mutations was identified in 73.9% of cases, with TP53 (56.1%), CDKN2A (8.9%), PIK3CA (8.9%), KRAS (4.5%) and EGFR (3.2%). Gene copy number alterations were identified in 75.8% of cases, including SOX2 amplification (31.2%), CDKN2A deletion (21.7%), PTEN deletion (16.6%), FGFR1 amplification (15.9%), EGFR amplification (14.0%), CCND1 amplification (14.0%), HER2 amplification (9.6%) and PDGFRA amplification (7.6%). Positive expression of VEGFR2 and PD-L1 and loss of PTEN expression were observed in 80.5%, 47.2%, and 42.7% of cases, respectively. Multivariate analysis showed that positive expression of PD-L1 was an independent favorable prognostic factor for DFS (HR = 0.610; P = 0.044). In conclusion, nearly all (93.6%) SqCLC cases harbored at least one potential druggable target. The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of SqCLC.
Insights
Nearly all squamous cell lung carcinoma (SqCLC) cases have actionable genetic targets. This study identified numerous mutations and copy number alterations, highlighting PD-L1 as a favorable prognostic factor for disease-free survival.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Squamous cell lung carcinoma (SqCLC) presents a significant challenge in cancer treatment.
- Identifying actionable genetic alterations is crucial for developing targeted therapies.
Purpose of the Study:
- To comprehensively analyze the genetic landscape of SqCLC.
- To identify potential therapeutic targets and prognostic biomarkers for SqCLC.
Main Methods:
- Next-generation sequencing (NGS) was used to identify somatic mutations in 50 genes.
- Fluorescence in situ hybridization (FISH) was employed to detect gene copy number alterations.
- Immunohistochemistry (IHC) was performed to assess protein expression of VEGFR2, PD-L1, and PTEN.
Main Results:
- Somatic mutations were found in 73.9% of SqCLC cases, with TP53 being the most frequent.
- Gene copy number alterations were present in 75.8% of cases, including SOX2 amplification and CDKN2A deletion.
- Positive PD-L1 expression was identified in 47.2% of cases and was an independent favorable prognostic factor for disease-free survival.
Conclusions:
- The vast majority (93.6%) of SqCLC cases harbor at least one potentially targetable genetic alteration.
- These findings support the development of precision medicine strategies for SqCLC.
- PD-L1 expression serves as a valuable prognostic biomarker in SqCLC.
