Comprehensive transcriptomic analysis of Papillary Thyroid Cancer: potential biomarkers associated with tumor progression [post]

2019 unpublished
20 Purpose: Identification of stage-specific prognostic/predictive biomarkers in papillary thyroid 21 carcinoma (PTC) could lead to its more efficient clinical management. The main objective of this 22 study was to characterize the stage-specific deregulation in genes and miRNAs expression in 23 PTC to identify potential prognostic biomarkers. 24 Methods: 495 RNASeq and 499 miRNASeq PTC samples (stage I-IV) as well as, respectively, 25 56 and 57 normal samples were retrieved from The Cancer
more » ... from The Cancer Genome Atlas (TCGA). Differential 26 expression analysis was performed using DESeq2 to identify deregulation of genes and miRNAs 27 between sequential stages. To identify the minority of patients who progress to higher stages, we 28 performed clustering analysis on stage I RNASeq data. An independent PTC RNASeq data set 29 (BioProject accession PRJEB11591) was also used for the validation of the results. 30 Results: LTF and PLA2R1 were identified as two promising biomarkers down-regulated in a 31 subgroup of stage I (both in TCGA and in the validation data set) and in the majority of stage IV 32 of PTC (in TCGA data set). hsa-miR-205, hsa-miR-509-2, hsa-miR-514-1 and hsa-miR-514-2 33 were also detected as up-regulated miRNAs in both PTC patients with stage I and stage III. 34 Hierarchical clustering of stage I samples showed substantial heterogeneity in the expression 35 pattern of PTC indicating the necessity of categorizing stage I patients based on the expressional 36 alterations of specific biomarkers. 37 Conclusion: stage I PTC patients showed large amount of expressional heterogeneity. Therefore 38 risk stratification based on the expressional alterations of candidate biomarkers could be an 39 important step toward personalized management of these patients. 40 41 The incidence of thyroid cancer has been increased worldwide during the past decades. 47 According to Globocan 2018, thyroid cancer is in ninth place for incidence with 567,000 cases 48 worldwide. It is 3 times more prevalent in women with the incidence rate of 10.2 per 100,000 49 [1]. Four major types of thyroid cancer, including Papillary (PTC), Follicular (FTC), Medullary 50 (MTC) and Anaplastic Thyroid Carcinoma (ATC) have already been characterized, among 51 which PTC is the most frequent histotype, comprising 85-90 % of all thyroid cancer cases. 52 Despite good prognosis, lymph node or distant metastasis is observed in approximately 10% of 53 PTC patients. Although it is still controversial, it has been suggested that there are specific PTC 54 subtypes related to the risk of locoregional recurrence or distant metastasis [2]. 55 Thyroid cancer staging provides prognostic information related to disease surveillance, 56 risk stratification and therapeutic strategies. Accurate initial staging requires detailed data 57 obtained from preoperative work up, intra operative findings and postoperative follow-up. 58 Moreover risk stratification based on clinical and pathology risk factors or molecular profiling 59 can be efficiently used to guide follow-up management decisions. According to the American 60 Joint Committee on Cancer (AJCC) TNM staging system, based on the size of tumor (T), spread 61 to nearby lymph nodes (N), and metastasis to distant sites (M), four stages for thyroid cancer (I-62 IV) can be specified. Moreover the staging system uses a combination of risk factors such as age 63 at diagnosis, size of the primary tumor, specific tumor histology, direct extension of the tumor to 64 the outside of thyroid gland, loco-regional metastases, and/or distant metastases to stratify
doi:10.21203/rs.2.15631/v1 fatcat:fbzvvimgczhevccine3papv2yu