Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
Cancer Med. 2013 Dec;2(6):836-48. doi: 10.1002/cam4.152. Epub 2013 Oct 31.
Cervical cancer is the second most common cancer among women worldwide, with developing countries accounting for >80% of the disease burden. Although in the West, active screening has been instrumental in reducing the incidence of cervical cancer, disease management is hampered due to lack of biomarkers for disease progression and defined therapeutic targets. Here we carried out gene expression profiling of 29 cervical cancer tissues from Indian women, spanning International Federation of Gynaecology and Obstetrics (FIGO) stages of the disease from early lesion (IA and IIA) to progressive stages (IIB and IIIA-B), and identified distinct gene expression signatures. Overall, metabolic pathways, pathways in cancer and signaling pathways were found to be significantly upregulated, while focal adhesion, cytokine-cytokine receptor interaction and WNT signaling were downregulated. Additionally, we identified candidate biomarkers of disease progression such as SPP1, proliferating cell nuclear antigen (PCNA), STK17A, and DUSP1 among others that were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the samples used for microarray studies as well in an independent set of 34 additional samples. Integrative analysis of our results with other cervical cancer profiling studies could facilitate the development of multiplex diagnostic markers of cervical cancer progression.
宫颈癌是全球女性中第二大常见的癌症,发展中国家承担了 >80%的疾病负担。尽管在西方,主动筛查在降低宫颈癌发病率方面发挥了重要作用,但由于缺乏疾病进展的生物标志物和明确的治疗靶点,疾病的管理受到了阻碍。在这里,我们对来自印度女性的 29 份宫颈癌组织进行了基因表达谱分析,涵盖了国际妇产科联合会(FIGO)疾病分期的早期病变(IA 和 IIA)到进展期(IIB 和 IIIA-B),并确定了独特的基因表达特征。总体而言,代谢途径、癌症途径和信号转导途径被发现显著上调,而粘着斑、细胞因子-细胞因子受体相互作用和 WNT 信号通路下调。此外,我们还鉴定出了一些疾病进展的候选生物标志物,如 SPP1、增殖细胞核抗原(PCNA)、STK17A 和 DUSP1 等,这些标志物在用于微阵列研究的样本以及另外 34 个独立样本的定量实时聚合酶链反应(qRT-PCR)中得到了验证。我们的研究结果与其他宫颈癌分析研究的综合分析,可以促进宫颈癌进展的多重诊断标志物的开发。