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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Thyroid Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1458956
This article is part of the Research Topic Advances in precision medicine in the management of thyroid nodules and thyroid cancer View all 35 articles

Investigation of risk signatures associated with anoikis in thyroid cancer through integrated transcriptome and Mendelian randomization analysis

Provisionally accepted
Xiang-Yi Chen Xiang-Yi Chen 1Jia-Ying Lai Jia-Ying Lai 1Wen-Jun Shen Wen-Jun Shen 1Dawei Wang Dawei Wang 2,3Zhixiao Wei Zhixiao Wei 1*
  • 1 Department of Nuclear medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, China
  • 2 Department of Medical Engineering, Medical Supplies Center of PLA General Hospital, Beijing, China
  • 3 Department of Nuclear Medicine, The sixth medical center of PLA General Hospital, Beijing, China

The final, formatted version of the article will be published soon.

    Background: Anoikis is intricately associated with the malignant progression of cancer. Thyroid cancer (THCA) is the most common endocrine tumor, metastasis is closely related to treatment response and prognosis of THCA. Hence, it is imperative to comprehensively identify predictive prognostic genes and novel molecular targets for effective THCA therapy. Methods: Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were utilized to mine differentially expressed anoikis-related (DE-ARGs). Then, the prognostic genes were identified and a risk signature was constructed for THCA using univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) method. Furthermore, the associations between risk signature and immune infiltration, immunotherapy, as well as potential mechanisms of action were determined using multiple R packages and Wilcoxon test. Finally, Mendelian randomized (MR) analysis was conducted to investigate the causal relationship between the prognostic genes and THCA. Results: In total, six prognostic genes (LRRC75A, METTL7B, ADRA1B, TPD52L1, TNFRSF10C, and CXCL8) related to anoikis were identified, and the corresponding risk signature were constructed to assess the survival time of THCA patients. Immunocorrelation analysis demonstrated the anoikis-relevant risk signature could be used to evaluate immunotherapy effects in THCA patients, and the infiltration of immune cells was correlated with the degree of risk in THCA patients. According to two-sample MR analysis, there was the significant causal relationship between CXCL8 and THCA (odds ratio [OR] > 1 & p < 0.05), and the increase of its gene expression would lead to an increased risk of THCA. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) confirmed the upregulated expression patterns of these prognostic genes in THCA tissues. Conclusion: In conclusion, we constructed the risk signature related to anoikis for THCA, which might have important clinical significance for improving the quality of life and treatment effect of THCA patients.

    Keywords: thyroid cancer, Anoikis, Risk signature, prognosis, Mendelian Randomization Analysis

    Received: 03 Jul 2024; Accepted: 17 Oct 2024.

    Copyright: © 2024 Chen, Lai, Shen, Wang and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhixiao Wei, Department of Nuclear medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.