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. 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. 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. 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.

中文翻译：

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鉴别潜在的新型生物标志物，以区分细胞学不确定的甲状腺恶性结节

细针穿刺活检广泛用于甲状腺癌结节的临床诊断评估，同时伴随较高的不确定性（15〜30％）来确定细胞学不确定病例的恶性程度。需要发现新的分子生物标记物以更精确地区分恶性甲状腺结节。我们采用加权基因共表达网络分析（WGCNA）来发现与细胞学不确定结节的恶性组织病理学显着相关的基因。此外，通过cBioportal和Geipa对甲状腺癌患者的样本进行了另一项独立调查，对鉴定出的重要基因进行了验证。涉及的重要基因的关键功能途径是通过GenClip blast。鉴定出二十四个签名基因与甲状腺结节恶性肿瘤显着相关。此外，突出显示了具有错义突变的五个新基因FN1（R534P），PROS1（（K200I），（Q571K）），SCEL（T320S），SLC34A2（T688M）和TENM1（S1131F），它们是排除结节恶性肿瘤的潜在生物标记物。已经确定，关键功能途径涉及甲状腺癌。这些结果将有助于更好地了解甲状腺结节恶性转化的机制，并表征甲状腺癌早期诊断的潜在生物标志物。已经确定，关键功能途径涉及甲状腺癌。这些结果将有助于更好地了解甲状腺结节恶性转化的机制，并表征甲状腺癌早期诊断的潜在生物标志物。已经确定，关键功能途径涉及甲状腺癌。这些结果将有助于更好地了解甲状腺结节恶性转化的机制，并表征甲状腺癌早期诊断的潜在生物标志物。