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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Evaluation of Raman spectroscopy for diagnosing EGFR mutation status in lung adenocarcinoma
Lei Wang1, Zhipei Zhang, Lijun Huang
1Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, No 1, Xinsi Road, Xi'an, Shaanxi Province 710038, China. lxfchest@fmmu.edu.cn (X.L.) niyunfng@fmmu.edu.cn (Y.N.).
Abstract:
Somatic mutations in the epidermal growth factor receptor (EGFR) gene were associated with sensitivity to small molecule tyrosine kinase inhibitors for patients with lung adenocarcinomas. In this research, EGFR mutation status was analyzed by DNA sequencing in 153 lung adenocarcinoma tissues. Of these, 75 samples carried EGFR mutations, including 29 with E19del mutation, 33 with L858R mutation, 7 with T790M mutation, and 6 with multiple mutations. Then, 30 samples including 10 with wild type (wt)-EGFR, 10 with L858R and 10 with E19del mutations were selected for Raman and immunohistochemistry (IHC) analyses. After removing the spectra from normal and non-mutated regions, 441 spectra were found appropriate for Raman analysis: 149 from wt-EGFR, 135 from L858R and 157 from E19del mutations. The Raman peaks at 675, 1107, 1127 and 1582 cm(-1) were significantly increased in wt-EGFR tissues which can be attributed to specific amino acids and DNA. The Raman peaks at 1085, 1175 and 1632 cm(-1) assigned to arginine were slightly increased in L858R tissues. The overall intensity of E19del tissues was weaker than others due to exon 19 deletion that removes residues 746-750 of the expressed protein. Principal component analysis (PCA) and support vector machine (SVM) were applied for final prediction. The PCA/SVM algorithm yielded an overall accuracy of 87.8% for diagnosing L858R or E19del from wt-EGFR tissues. Finally, RS provides a simple, rapid and low-cost procedure based upon the molecular signatures for predicting EGFR mutation status.
Insights
Raman spectroscopy (RS) can rapidly and affordably predict epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. This molecular signature analysis offers a new diagnostic approach for non-small cell lung cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Somatic mutations in the epidermal growth factor receptor (EGFR) gene are crucial for targeted therapy in lung adenocarcinomas.
- EGFR mutations, including E19del and L858R, predict sensitivity to tyrosine kinase inhibitors.
- Accurate and rapid detection of EGFR mutation status is essential for effective patient treatment.
Purpose of the Study:
- To investigate the potential of Raman spectroscopy (RS) for predicting EGFR mutation status in lung adenocarcinoma tissues.
- To identify specific molecular signatures associated with wild-type (wt)-EGFR, L858R, and E19del mutations using RS.
- To develop a rapid, low-cost method for EGFR mutation prediction.
Main Methods:
- DNA sequencing was used to determine EGFR mutation status in 153 lung adenocarcinoma tissues.
- Selected samples (wt-EGFR, L858R, E19del) underwent Raman spectroscopy and immunohistochemistry (IHC) analysis.
- Principal Component Analysis (PCA) and Support Vector Machine (SVM) algorithms were applied to Raman spectra for classification.
Main Results:
- Distinct Raman spectral features were observed for wt-EGFR, L858R, and E19del mutations.
- Specific Raman peaks at 675, 1107, 1127, and 1582 cm⁻¹ were increased in wt-EGFR tissues.
- Raman peaks at 1085, 1175, and 1632 cm⁻¹ (arginine-related) were slightly increased in L858R tissues.
- The PCA/SVM algorithm achieved 87.8% accuracy in differentiating L858R/E19del from wt-EGFR tissues.
Conclusions:
- Raman spectroscopy provides a simple, rapid, and low-cost method for predicting EGFR mutation status in lung adenocarcinoma.
- Molecular signatures identified by RS can serve as a basis for a novel diagnostic approach.
- This technique has the potential to aid in the clinical management of lung cancer patients.
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