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Comprehensive characterization of pathological stage-related genes of papillary thyroid cancer along with survival prediction
Authors:Lei Xu  Feng Liu  Haiyan Li  Menglong Li  Yongmei Xie  Zhihui Li  Yanzhi Guo
Institution:1. College of Chemistry, Sichuan University, Chengdu, China

Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Software (equal), Validation (equal), Writing - original draft (equal);2. Department of Thyroid Surgery, West China Hospital of Sichuan University, Chengdu, China

Contribution: Data curation (equal), ?Investigation (equal), Methodology (equal), Resources (equal), Supervision (equal);3. College of Chemistry, Sichuan University, Chengdu, China

Contribution: Data curation (equal), Methodology (equal), Resources (equal);4. College of Chemistry, Sichuan University, Chengdu, China

Contribution: Methodology (equal), Resources (equal), Validation (equal);5. Department of Thyroid Surgery, West China Hospital of Sichuan University, Chengdu, China

Contribution: Data curation (equal), Methodology (equal), Resources (equal);6. Department of Thyroid Surgery, West China Hospital of Sichuan University, Chengdu, China;7. College of Chemistry, Sichuan University, Chengdu, China

Abstract:It is crucial to understand the differences across papillary thyroid cancer (PTC) stages, so as to provide a basis for individualized treatments. Here, comprehensive function characterization of PTC stage-related genes was performed and a new prognostic signature was developed for advanced patients. Two gene modules were confirmed to be closely associated with PTC stages and further six hub genes were identified that yield excellent diagnostic efficiency between tumour and normal tissues. Genetic alteration analysis indicates that they are much conservative since mutations in the DNA of them rarely occur, but changes of DNA methylation on these six genes show that 12 DNA methylation sites are significantly associated with their corresponding genes' expression. Validation data set testing also suggests that these six stage-related hub genes would be probably potential biomarkers for marking four stages. Subsequently, a 21-mRNA-based prognostic risk model was constructed for PTC stage III/IV patients and it could effectively predict the survival of patients with strong prognostic ability. Functional analysis shows that differential expression genes between high- and low-risk patients would promote the progress of PTC to some extent. Moreover, tumour microenvironment (TME) of high-risk patients may be more conducive to tumour growth by ESTIMATE analysis.
Keywords:hub gene  papillary thyroid cancer  prognostic risk model  tumour stage
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