Target-based molecular signature characteristics of cervical adenocarcinoma and squamous cell carcinoma
Target-based molecular signature characteristics of cervical adenocarcinoma and squamous cell carcinoma
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DOI：
10.3892/ijo.2013.1961
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发表时间：
2013-08-01
影响因子：
5.2
通讯作者：
Ahn, Woong Shick
中科院分区：
文献类型：
--
作者：
Kim, Yong-Wan;Bae, Su Mi;Ahn, Woong Shick
目前迫切需要对子宫颈癌(AC)和鳞癌(SCC)进行分子标记研究。这项研究利用寡聚微阵列和通路分析来表征与AC和SCC相关的分子网络的转录特征。利用10K寡核苷酸芯片分析了28例宫颈癌患者和17例正常宫颈组织中差异表达的潜在转录本。使用基因组学工具对分子网络进行关联，以在全球范围内探索细胞路径。46个转录本的基因表达水平将癌症样本分为AC组和SCC组。KRT17、IGEBP2、Calca和VIPR1基因在AC和SCC中有差异表达。此外，我们发现了一个转录转录信号，它可以根据肿瘤的细胞过程预测肿瘤的分类和进展。鳞状细胞癌的下调特征是嗜铬细胞瘤细胞死亡(P=0.0037)、神经元凋亡(P=0.009)和DNA损伤(P=0.0038)。相反，AC的分子特征是免疫紊乱(P=0.006)、脾肿大(P=0.0053)和肝脏系统紊乱(P=0.006)。研究发现，G2/M DNA损伤检查点调控通路(P=0.05)与IGF1R显著相关，IGF1R是鳞癌细胞质信号转导通路中的一个新的调控成分。相反，抗原呈递的典型途径(P=0.038)似乎与AC中的PPARγ相关联。综上所述，这些实验提供了关于分子网络可能通过两条独立的途径在调节鳞癌和AC中的作用的重要新信息，并有助于为宫颈癌的预防和治疗提供新的靶点。
There is an urgent need for molecular marker studies of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix. This study utilized oligomicroarray and pathway analyses to characterize a transcriptomic signature with molecular networks associated with AC and SCC. A 10K oligomicroarray was used to identify potential transcripts that were differentially expressed in cervical cancers from 28 patients and common reference RNAs from 17 different normal cervixes. Molecular networks were correlated using genomics tools to globally explore cellular pathways. Gene expression levels of 46 transcripts separated cancer samples into AC and SCC groups. Genes including: KRT17, IGEBP2, CALCA and VIPR1 were differentially expressed in AC and SCC. In addition, we identified a transcriptomic signature that predicted tumor classification and progression based upon its cellular processes. The downregulated signatures for SCC were cell death of pheochromocytoma cells (P=0.0037), apoptosis of neurons (P=0.009) and damage to DNA (P=0.0038). By contrast, the upregulated molecular signatures in AC were immunological disorder (P=0.006), splenomegaly (P=0.0053) and hepatic system disorder (P=0.006). The G2/M DNA damage checkpoint regulation pathway (P=0.05) was found to be significantly linked to IGF1R as a new regulatory component of a putative cytoplasmic signaling cascade in SCC. By contrast, the antigen presenting canonical pathway (P=0.038) appeared to be linked to PPAR gamma in AC. Taken together, these experiments provide important new information regarding the role of molecular networks in mediating SCC and AC, possibly through two independent pathways, and contribute to provide new targets for the prevention and treatment of cervical cancer.