Subtyping Lung Cancer Using DNA Methylation in Liquid Biopsies

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Lung cancer (LCa) is a leading cause of cancer-related death globally.
• Accurate histopathological subtyping is crucial for LCa treatment and prognosis.
• Invasive procedures for diagnosis can be insufficient, highlighting the need for alternative methods.

Purpose of the Study:

• To evaluate the methylation status of specific genes in circulating cell-free DNA (ccfDNA) from LCa patients.
• To determine the accuracy of ccfDNA methylation for distinguishing between LCa subtypes.

Main Methods:

• Quantitative methylation-specific PCR was used to assess methylation levels of APC, HOXA9, RARβ2, and RASSF1A.
• Three independent study groups, including tissue and plasma samples, were analyzed.
• Non-parametric tests and ROC curve analysis were employed to evaluate associations and diagnostic accuracy.

Main Results:

• HOXA9 and RASSF1A methylation levels were significantly higher in small-cell lung cancer (SCLC) compared to non-small-cell lung cancer (NSCLC) in plasma samples.
• HOXA9 demonstrated high sensitivity (63.8%) and RASSF1A showed high specificity (96.2%) for SCLC detection.
• HOXA9 methylation was also found to be higher in squamous cell carcinoma than in adenocarcinoma in tissue samples.

Conclusions:

• Methylation analysis of selected genes in ccfDNA presents a promising minimally invasive approach for LCa subtyping.
• This method can serve as a valuable adjunct to conventional diagnostic procedures.
• ccfDNA methylation analysis aids in improving the diagnostic accuracy and therapeutic guidance for lung cancer.