High RPMB predicts poor disease-free survival of male N1 papillary thyroid cancer after adjuvant radioiodine therapy

Abstract

The current recommendation for the use of adjuvant radioactive iodine (RAI) therapy in papillary thyroid cancer (PTC) after radical surgery is based on clinicopathological factors; however, this recommendation remains controversial. Our present study established a new biomarker, RPMB (promotor methylation burden of DNA repair genes (DRGs)), to identify a patient subgroup suitable for adjuvant RAI therapy. We defined RPMB as the ratio of methylated DRGs to the total number of DRGs. Methylation profiles of 498 PTC tumors and their clinical data were retrieved from the Cancer Genome Atlas (TCGA) database. DRGs of PTC subjects were found to be much more hypomethylated than controls across the whole profile (all p < 0.001). PTC patients with higher RPMBs tended to be ≥45 years old and female, and these PTCs were commonly unifocal, with N0 disease, wild-type BRAF, and mutated RAS. The subgroup analysis indicated that high RPMBs were significantly associated with poor disease-free survival (DFS) in male patients with PTC (HR = 4.855, 95% CI: 1.527–15.433, p = 0.007). Moreover, Kaplan–Meier analysis showed that high RPMBs could significantly predict poor DFS in male patients after R0 resection for N1 disease (HR: 5.431, 95% CI: 1.045–28.219, p = 0.024), and the p-value was very close to significance in these patients after adjuvant RAI therapy (HR: 6.269, 95% CI: 0.693–56.714, p = 0.062). Multivariate analysis indicated that both male sex (HR = 14.565, 95%CI: 2.153–98.507, p = 0.006) and high RPMBs (HR = 11.206, 95%CI: 1.622–77.405, p = 0.014) were independent unfavorable factors for DFS after adjuvant RAI therapy. Therefore, RPMB might be a potential predictor for identifying suitable male patients with PTC who can benefit from adjuvant RAI therapy.