Plasma cell-free DNA methylation combined with tumor mutation detection in prognostic prediction of patients with non-small cell lung cancer (NSCLC)

Abstract

Background: Lung Cancer is one of the most common cancers with high degree of malignancy, is a devastating disease with a poor prognosis worldwide. prognostic prediction for patients with non small-cell lung cancer (NSCLC) is still challenge.

Material and methods: The cohort consisted of 64 consecutive patients with NSCLC identified from June1, 2014, to June 30, 2018. Liquid biopsy samples were collected. Genomic mutation DNA was calculated by including all substitutions and indels over the entire somatic, coding, sequencing length. statistical evaluations were carried out using SPSS software.

Results: Quantity of total ctDNA was successfully determined in all 64 patients from whom baseline circulating DNA was available. ctDNA concentration ranged from 4000 to 3,562,000 genome equivalents per milliliter. Treatments induced a significant decrease in cancer specific markers in most patients with response to treatments, while the methylated DNA demonstrated favorable prediction efficiency regardless of the response status. Patients with ctDNA mutation and methylated DNA decreasing have favorable overall survival (P < .05). combination of genetic and methylated DNA decreasing had high reliability in predicting overall survival of patients with NSCLC.

Conclusions: We have detected both tumor mutations and methylated DNA in plasma of patients with NSCLC. Combined genetic and methylated DNA decreasing after treatment was an independent risk factor for prognosis of patients with NSCLC. Meanwhile, it had favorable predict value and had potential to be defined as a novel biomarker for patients with NSCLC.

Figure 1

A, genomic mutational detection in all 64 patients with non-small-cell lung cancer and the ctDNA concentration ranged from 4000 to 3,562,000 genome equivalents per milliliter; B: Quantity of methylated DNA could be determined in all 64 samples and ranged from 3300 to 2,394,000 /mL.

Figure 2

Dynamic changing of both mutational DNA and methylated DNA. A. mutational DNA was significant decreasing in the group with PFS > 3 months; B: methylated DNA was significant decreasing in both the group with PFS > 3 months and PFS < 3 months; C: individual with tumor mutation changing after treatment; D: individual with methylated DNA changing after treatment.

Figure 3

Survival analysis of factors related with OS. A: tumor mutation decreasing was associated with favorable OS in patients with non-small-cell lung cancer ; B: methylated DNA decreasing was associated with favorable OS in patients with non-small-cell lung cancer ; C: combined mutational DNA and methylated DNA have a much favorable survival compared with other patients.

Figure 4

Predictive performance of mutational DNA decreased (36 patients), methylated DNA decreased (38 patients), and combined mutational DNA and methylated DNA decreased have significant difference in predicting prognosis of patients with non-small-cell lung cancer.