Gao Luying, Liu Ruifeng, Xia Yu, Pan Aonan, Shi Xinlong, Ma Liyuan, Ji Jiang, Hu Ya, Li Xiaoyi, An Yuang, Luo Nengwen, Liang Zhiyong, Zhou Liangrui, Jiang Yuxin
Department of Ultrasound, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Cancer. 2024 Feb 25;15(8):2206-2213. doi: 10.7150/jca.92656. eCollection 2024.
To explore the potential value of a novel marker, KIF-12, in the progression and prognosis of papillary thyroid carcinoma (PTC) through integrative bioinformatics analysis, and clinical sample validation of the prognostic value of KIF-12. We extracted the clinicopathological data of 502 PTC patients from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) dataset to identify reliable differentially expressed genes (DEGs) between high and low KIF12 expression groups. Functional enrichment analysis was performed on upregulated DEGs. Gene set enrichment analysis (GESA) was performed to identify the biological pathways. We further applied Cox analysis to determine independent risk factors associated with the PTC progression-free interval (PFI), and a nomogram was established to predict disease outcome. Finally, the prognostic value of KIF12 was validated by means of clinical samples from PTC patients with and without lateral lymph node metastasis. On the basis of the TCGA-THCA database, we found that low KIF-12 expression was significantly related to a higher TNM stage (p<0.05), BRAF mutation status (p = 0.019), and extrathyroidal extension (p<0.001). KIF-12 was an independent prognostic factor of PTC (OR=0.319, 95% CI=0.130-0.784, P=0.013). The prognostic value of KIF12 was also successfully validated in clinical samples from twenty-nine PTC patients with lateral lymph node metastasis by comparison with twenty-two PTC patients without lymph node metastasis (P = 0.004). We report that KIF-12 has a tumor suppressive function in PTC and may be a useful prognostic tool to predict patient outcomes.
通过综合生物信息学分析以及对KIF-12预后价值的临床样本验证,探讨新型标志物KIF-12在甲状腺乳头状癌(PTC)进展和预后中的潜在价值。我们从癌症基因组图谱-甲状腺癌(TCGA-THCA)数据集中提取了502例PTC患者的临床病理数据,以确定KIF12高表达组和低表达组之间可靠的差异表达基因(DEG)。对上调的DEG进行功能富集分析。进行基因集富集分析(GESA)以确定生物学途径。我们进一步应用Cox分析来确定与PTC无进展生存期(PFI)相关的独立危险因素,并建立了列线图来预测疾病结局。最后,通过来自有和无侧方淋巴结转移的PTC患者的临床样本验证KIF12的预后价值。基于TCGA-THCA数据库,我们发现KIF-12低表达与更高的TNM分期(p<0.05)、BRAF突变状态(p = 0.019)和甲状腺外侵犯(p<0.001)显著相关。KIF-12是PTC的独立预后因素(OR=0.319,95%CI=0.130-0.784,P=0.013)。通过与22例无淋巴结转移的PTC患者比较,KIF12的预后价值也在29例有侧方淋巴结转移的PTC患者的临床样本中得到成功验证(P = 0.004)。我们报告KIF-12在PTC中具有肿瘤抑制功能,可能是预测患者结局的有用预后工具。