A friend recently performed a chest CT in a local hospital and found an 8mm ground glass nodule in the right middle lung. At the same time, he did a self-funded test of pulmonary nodule DNA methylation under the doctor’s recommendation. , the test result was grade 4, indicating the possibility of malignancy. This friend was very nervous about this result. He didn’t know if this pulmonary nodule needed surgery as soon as possible, so he came to me for consultation. After seeing his CT scans and methylation results, he was finally advised to continue follow-up.
What is pulmonary nodule methylation testing? Why test it to know if you are at risk of cancer?
DNA methylation, as a relatively stable genetic modification state, can be passed on to the next generation of DNA along with the DNA replication process, and is an important genetic mechanism. DNA methylation is like putting a magic “hat” on the gene that enables cancer genes to remain silent. However, if DNA methylation is abnormal, it will easily activate oncogenes and inactivate tumor suppressor genes. Therefore, abnormal methylation is one of the important epigenetic modifications in the occurrence and development of cancer. Abnormal DNA methylation is a characteristic of tumors. one.
As early as 2005, Schmiemann et al. of Heine University in Germany found that the methylation status of RASSF1A, APC, p16 (INK4a) and other genes was abnormal in lung cancer patients, so they proposed To use methylation detection for early diagnosis of lung cancer. Therefore, DNA methylation detection is of great significance for the judgment of benign and malignant pulmonary nodules and the judgment of tumor malignancy.
In the early stage of lung cancer, the tumor cells release very little into the blood, and the probability of directly detecting circulating tumor cells is relatively low, but the DNA fragments released after apoptosis may enter the blood, which is ctDNA. Detection of lung cancer-specific methylated DNA in plasma can assist in the determination of benign and malignant pulmonary nodules. The development of next-generation DNA sequencing technology has also made this detection possible.
The initial exploration of ctDNA methylation detection for the identification of benign and malignant pulmonary nodules was completed by the team of Academician Zhong Nanshan and Professor He Jianxing in conjunction with Standard Medical. A total of 132 patients with pulmonary nodules who underwent surgery and 118 normal controls were included. After taking 10ml of plasma, ctDNA detection was performed, and methylation abnormalities at 9 sites were developed as a diagnostic model. The results show that the sensitivity and specificity in early stage lung cancer are about 80%. Based on the preliminary exploration results, the team of Academician Zhong Nanshan has since developed a large-scale lung nodule ctDNA identification research project “Zhongsheng Project”, which included about 10,000 pulmonary nodules, including a large number of stage IA, minimally invasive carcinoma and primary pulmonary nodules. cancer.
Pulmonary nodule DNA methylation results are divided into 5 grades:
Grade 1: It indicates a benign nodule with no obvious abnormality. It is recommended to perform a physical examination every two years, supplemented by the detection of benign and malignant pulmonary nodules.
Grade 2: It indicates a benign nodule, but the body tends to be sub-healthy. It is recommended to perform a physical examination once a year, supplemented by the detection of benign and malignant pulmonary nodules.
Grade 3: It is suggested that it may be a benign nodule, but there is corresponding data indicating that the sample test results have the risk of lung cancer in this interval.
Grade 4: It indicates that the pulmonary nodule has a low risk of malignancy. It is recommended to follow up closely and make further diagnosis under the guidance of a doctor according to individual circumstances.
Grade 5: It indicates that the pulmonary nodule has a high risk of malignancy. It is recommended to do further examination under the guidance of a doctor, or to increase the frequency of follow-up.
Does the methylation test of pulmonary nodules reach grade 4-5, it must be malignant? No, as any detection method, it has its limitations, and there may be false positives and false negatives. Therefore, the methylation test results can only be used as an evaluation reference, which needs to be combined with imaging examinations for comprehensive judgment. For suspected high-risk nodules, the follow-up time should be shortened as much as possible. For low-risk nodules assessed by imaging, even if the methylation test reaches grade 3-5, there is no need to worry too much, and regular re-examination is enough.