尽管在过去的几十年中对甲状腺乳头状癌(PTC)进行了许多研究,一些关键和重要的基因仍未被发现。为了探索可能在PTC中起关键作用的基因,对表达水平的详细分析,突变,并对激肽释放酶相关肽酶(KLKs)家族基因在PTC中的临床意义进行了研究,为该病的精确治疗提供了新的靶点。使用各种在线工具对KLK家族基因进行了全面分析,比如GEPIA,Kaplan-Meier绘图仪,LinkedOmics,GSCA,TIMER,和Cluego.KLK7、KLK10和KLK11是KLK家族基因的关键因子。然后,在KLK7/10/11上进行功能测定以确定其增殖,迁移,以及PTC的入侵能力。甲状腺癌中KLK7、KLK10、KLK11、KLK13mRNA表达水平显著升高,而KLK1、KLK2、KLK3和KLK4mRNA水平较正常组织降低。在甲状腺癌中还观察到KLK2/7-12/15表达水平与肿瘤分期之间的相关性。生存分析表明,KLK4/5/7/9-12/14与甲状腺癌患者的总生存有关。KLK基因不仅与癌症相关通路密切相关,但KLK7/10/11也与免疫细胞浸润相关。最后,沉默KLK7/10/11人甲状腺乳头状癌细胞生长受损,迁移能力,和侵入性。KLK7、KLK10和KLK11的表达增加可作为鉴别PTC患者的分子标志物。KLK7、KLK10和KLK11可能是PTC精准治疗的潜在预后指标和靶点。
Despite many studies on papillary thyroid carcinoma (PTC) in the past few decades, some critical and significant genes remain undiscovered. To explore genes that may play crucial roles in PTC, a detailed analysis of the expression levels, mutations, and clinical significance of Kallikrein-related peptidases (KLKs) family genes in PTC was undertaken to provide new targets for the precise treatment of the disease. A comprehensive analysis of KLK family genes was performed using various online tools, such as GEPIA, Kaplan-Meier Plotter, LinkedOmics, GSCA, TIMER, and Cluego. KLK7, KLK10, and KLK11 were critical factors of KLK family genes. Then, functional assays were carried out on KLK7/10/11 to determine their proliferation, migration, and invasion capabilities in PTC. The mRNA expression levels of KLK7, KLK10, KLK11, and KLK13 were significantly elevated in thyroid carcinoma, while KLK1, KLK2, KLK3 and KLK4 mRNA levels were decreased compared to normal tissues. Correlations between KLK2/7-12/15 expression levels and tumor stage were also observed in thyroid carcinoma. Survival analysis demonstrated that KLK4/5/7/9-12/14 was associated with overall survival in patients with thyroid cancer. Not only were KLK genes strongly associated with cancer-related pathways, but also KLK7/10/11 was associated with immune-cell infiltration. Finally, silencing KLK7/10/11 impaired human papillary thyroid carcinoma cells\' growth, migration ability, and invasiveness. The increased expression of KLK7, KLK10, and KLK11 may serve as molecular markers to identify PTC patients. KLK7, KLK10, and KLK11 could be potential prognostic indicators and targets for precision therapy against PTC.