• J. Clin. Endocrinol. Metab. · Sep 2019

    Transcriptome Analyses Identify a Metabolic Gene Signature Indicative of Dedifferentiation of Papillary Thyroid Cancer.

    • Ben Ma, Hongyi Jiang, Duo Wen, Jiaqian Hu, Litao Han, Wanlin Liu, Weibo Xu, Xiao Shi, Wenjun Wei, Tian Liao, Yulong Wang, Zhongwu Lu, Yu Wang, and Qinghai Ji.
    • Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
    • J. Clin. Endocrinol. Metab. 2019 Sep 1; 104 (9): 3713-3725.

    ContextMetabolic reprogramming is a common feature of tumorigenesis. It remains unknown concerning the expression pattern of metabolism-associated genes in dedifferentiated thyroid cancer (DDTC).ObjectiveThis study aimed to identify a useful signature to indicate dedifferentiation of papillary thyroid cancer (PTC).Design And SettingWe used one discovery and two validation cohorts to screen out aberrant metabolic genes in DDTC, and further used The Cancer Genome Atlas (TCGA) cohort to search for independent risk factors for the low-differentiated phenotype of PTC as a signature of dedifferentiation. The prediction of the signature for DDTC was validated in the TCGA cohort and the combined Gene Expression Omnibus cohort. We also analyzed the correlations of the signature risk score with clinicopathological features of PTC. Gene set enrichment analyses were performed in the TCGA cohort.ResultsSignificant enrichment of metabolic pathways correlated with differentiation status of PTC. A signature of metabolic genes including LPCAT2, ACOT7, HSD17B8, PDE8B, and ST3GAL1 was discovered and validated across three cohorts. The signature was not only predictive of DDTC but also significantly associated with BRAFV600E mutation (P < 0.001), T3/T4 stage (P < 0.001), extrathyroidal extension (P < 0.001), lymph node metastasis (P < 0.001), and tumor/lymph node/metastasis III/IV stage (P < 0.001) in PTC. Downregulations of LPCAT2 expression (P = 0.009) and ST3GAL1 expression (P = 0.005) increased risks of decreased disease-free survival for patients. Furthermore, the signature was implicated in a number of oncogenic biological pathways.ConclusionsOur findings suggest that metabolic deregulations mediate dedifferentiation of PTC, and that the metabolic gene signature can be used as a biomarker for DDTC.Copyright © 2019 Endocrine Society.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…