The Updated AJCC/TNM Staging System for Papillary Thyroid Cancer (8th Edition): From the Perspective of Genomic Analysis.

Abstract

Recently, the American Joint Committee on Cancer published the 8th edition of its Cancer Staging Manual with major changes regarding the staging of thyroid cancer, including the raising of the age cutoff from 45 to 55 years. Using the clinical and genetic data of 505 papillary thyroid cancer (PTC) cases, we aimed to compare overall survival (OS) and recurrence-free survival (RFS) with different age cutoff values, and also investigate the efficacy of the new staging system on a genomic level. We downloaded gene expression data, somatic mutation profile, copy number alteration data and clinical data of 505 PTC patients from The Cancer Genome Atlas data portal. We used multiple statistical analysis and multiplatform genomic analysis to evaluate the efficacy of the 8th edition. When using 55 years as the cutoff value for analyzing RFS, the Kaplan-Meier plot showed a significant p value but not when using 45 years (p = 0.006 vs. p = 0.493), but both cutoff values were significant when analyzing OS (p = 1.1 × 10^-9 with age 55 vs. p = 4.4 × 10^-5 with age 45). When looking at stage-dependent survival, both the 7th and 8th edition had significant p values (p = 0.048 vs. p = 3.1 × 10^-9 in RFS and p = 5.9 × 10^-10 vs. p = 2.2 × 10^-10 in OS). Multiplatform genomic analysis showed patients ≥55 years had 103 differently expressed genes when compared with other age groups. Signaling pathway analysis revealed that patients ≥55 years had altered pathways associated with aggressiveness of thyroid cancer. In conclusion, this is the first study to show clinical and genetic evidence supporting the altered age cutoff point of 55 years in the AJCC 8th edition for PTC patients.