Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Sci Rep. 2018 Jan 31;8(1):2007. doi: 10.1038/s41598-017-19010-5.
Metastasis of head and neck tumors is responsible for a high mortality rate. Understanding its biochemistry may allow insights into tumorigenesis. To that end we carried out RNA-Seq analyses of 5 SCC9 derived oral cancer cell lines displaying increased invasive potential. Differentially expressed genes (DEGs) were annotated based on p-values and false discovery rate (q-values). All 292 KEGG pathways related to the human genome were compared in order to pinpoint the absolute and relative contributions to the invasive process considering the 8 hallmarks of cancer plus 2 new defined categories, as well as we made with our transcriptomic data. In terms of absolute contribution, the highest correlations were associated to the categories of evading immune destruction and energy metabolism and for relative contributions, angiogenesis and evading immune destruction. DEGs were distributed into each one of all possible modes of regulation, regarding up, down and continuum expression, along the 3 stages of metastatic progression. For p-values twenty-six genes were consistently present along the tumoral progression and 4 for q-values. Among the DEGs, we found 2 novel potentially informative metastatic markers: PIGG and SLC8B1. Furthermore, interactome analysis showed that MYH14, ANGPTL4, PPARD and ENPP1 are amenable to pharmacological interventions.
头颈部肿瘤的转移是导致高死亡率的主要原因。了解其生物化学特性可能有助于深入了解肿瘤的发生机制。为此,我们对 5 种具有侵袭性潜能的 SCC9 衍生口腔癌细胞系进行了 RNA-Seq 分析。根据 p 值和错误发现率 (q 值) 对差异表达基因 (DEG) 进行注释。比较了与人类基因组相关的所有 292 个 KEGG 通路,以确定绝对和相对贡献,考虑到癌症的 8 个标志性特征加上我们根据转录组数据定义的 2 个新类别,考虑到癌症的 8 个标志性特征加上我们根据转录组数据定义的 2 个新类别。就绝对贡献而言,与逃避免疫破坏和能量代谢相关的类别具有最高的相关性,而相对贡献与血管生成和逃避免疫破坏相关。根据上调、下调和连续表达,将 DEG 分配到转移进展的 3 个阶段中的每一个可能的调控模式中。在 p 值方面,有 26 个基因在肿瘤进展过程中始终存在,而 q 值则有 4 个。在差异表达基因中,我们发现了 2 个新的潜在有信息的转移标记物:PIGG 和 SLC8B1。此外,相互作用分析表明,MYH14、ANGPTL4、PPARD 和 ENPP1 可进行药物干预。