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

[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.