The prognostic value of a Methylome-based Malignancy Density Scoring System to predict recurrence risk in early-stage Lung Adenocarcinoma.

Theranostics
Lu YangYan Wang

Abstract

Current NCCN guidelines do not recommend the use of adjuvant chemotherapy for stage IA lung adenocarcinoma patients with R0 surgery. However, 25% to 40% of patients with stage IA disease experience recurrence. Stratifying patients according to the recurrence risk may tailor adjuvant therapy and surveillance imaging for those with a higher risk. However, prognostic markers are often identified by comparing high-risk and low-risk cases which might introduce bias due to the widespread interpatient heterogeneity. Here, we developed a scoring system quantifying the degree of field cancerization in adjacent normal tissues and revealed its association with disease-free survival (DFS). Methods: We recruited a cohort of 44 patients with resected stage IA lung adenocarcinoma who did not receive adjuvant therapy. Both tumor and adjacent normal tissues were obtained from each patient and subjected to capture-based targeted genomic and epigenomic profiling. A novel methylome-based scoring system namely malignancy density ratio (MD ratio) was developed based on 39 patients by comparing tumor and corresponding adjacent normal tissues of each patient. A MD score was then obtained by Wald statistics. The correlations of MD ratio, MD score, and ...Continue Reading

Methods Mentioned

BETA
BS-seq
methylation profiling
PCR
surgical resection

Software Mentioned

Trimmomatic
sambamba
BWA aligner
meth
FACTERA
Genome Analysis ToolKit ( GATK )
BWA
samblaster
R

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