Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks

Abstract Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we performed an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling revealed that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4 - RET were enriched by the high RR. Integrative multi-omics analysis further described the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineated dominated molecular patterns of different RRs. Moreover, the PTC patients were clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes displayed significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.