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Background  The fine-needle aspiration (FNA) biopsy was broadly applied to clinical diagnostics evaluation for thyroid carcinomas nodule, while companioning with higher uncertainty rate (15~30%) to identify malignancy for cytological indeterminate cases. It is requirement to discover novel molecular biomarkers to differentiate malignant thyroid nodule more precise.    Methods  We employed weighted gene co-expression network analysis (WGCNA) to discover genes significantly associated with malignant histopathology for cytological indeterminate nodules. In addition, identified significantly genes were validated through another independently investigations of thyroid carcinomas patient’s samples via cBioportal and Geipa. The key function pathways of significant genes involving were blast through GenClip.    Results  Twenty-four signature genes were identified significantly related to thyroid nodules malignancy. Furthermore, five novel genes with missense mutation,  FN1  (R534P),  PROS1 ((K200I), (Q571K)),  SCEL  (T320S),  SLC34A2 (T688M) and  TENM1  (S1131F), were highlighted as potential biomarkers to rule out nodules malignancy. It was identified that the key functional pathways involving in thyroid carcinomas.    Conclusion  These results will be helpful to better understand the mechanism of thyroid nodules malignant transformation and characterize the potentially biomarkers for thyroid carcinomas early diagnostics.

Identification of potential novel biomarkers to differentiate malignant thyroid nodules with cytological indeterminate