Department of Dermatology, PLA General Hospital, Beijing, China.
Dermatological Department, Tianjin Fifth Centre Hospital, Tianjin, China.
FEBS Open Bio. 2020 Aug;10(8):1577-1586. doi: 10.1002/2211-5463.12912. Epub 2020 Jul 13.
Global efforts have been undertaken to define the genome-wide distribution of epigenetic markers in cancerous tissues, which provide an invaluable opportunity to understand cancer biology and identify predictive signatures. Several studies have focused on the gene expression patterns of squamous carcinoma to identify tumor subtypes and find prognostic and therapeutic targets because squamous carcinoma genomes showed high instability. However, the number of reliable reports referring prognostic significance of genes and their role in squamous carcinoma is still quite limited. Krüppel-like factor 7 (KLF7) is a transcription factor that is widely expressed in numerous human tissues at low levels. Members of the KLF family have established roles in tumor cell fate, stress response, cell survival and the tumor-initiating properties of cancer stem-like cells. Hence to investigate whether KFL7 expression from cancer tissue holds promise as a prognostic and/or therapeutic target, we analyzed gene expression profiles from squamous carcinoma and surgical margin tissues in The Cancer Genome Atlas. We identified significant up-regulation of KLF7 in squamous carcinoma, which was confirmed by immunohistochemical staining. Elevated KLF7 expression was associated with poor squamous carcinoma prognosis before and after correcting for confounding factors by multivariate Cox regression analysis. Several pathways, such as Neurotrophin and GnRH pathways, were activated in KLF7-up-regulated squamous carcinoma samples through Gene Set Enrichment Analysis. In conclusion, we consolidate the potential role(s) of KLF7 in squamous carcinoma carcinogenesis from The Cancer Genome Atlas surgical margin tissue, offering insights into expression signatures that are potentially useful for prognosis modalities.
全球范围内已经开展了许多努力，旨在定义癌症组织中表观遗传标记的全基因组分布，这为理解癌症生物学和识别预测性标志物提供了宝贵的机会。几项研究集中在鳞状细胞癌的基因表达模式上，以识别肿瘤亚型并找到预后和治疗靶点，因为鳞状细胞癌的基因组显示出高度的不稳定性。然而，能够可靠地报告基因的预后意义及其在鳞状细胞癌中的作用的研究仍然相当有限。Krüppel 样因子 7（KLF7）是一种在许多人类组织中广泛表达的转录因子，表达水平较低。KLF 家族的成员在肿瘤细胞命运、应激反应、细胞存活和癌症干细胞样细胞的肿瘤起始特性中发挥着重要作用。因此，为了研究癌症组织中 KFL7 的表达是否有望成为预后和/或治疗靶点，我们分析了癌症基因组图谱中鳞状细胞癌和手术边缘组织的基因表达谱。我们发现 KLF7 在鳞状细胞癌中显著上调，免疫组织化学染色证实了这一点。多变量 Cox 回归分析校正混杂因素后，KLF7 表达升高与鳞状细胞癌预后不良相关。通过基因集富集分析，发现 KLF7 上调的鳞状细胞癌样本中激活了几个途径，如神经递质和 GnRH 途径。总之，我们从癌症基因组图谱手术边缘组织中整合了 KLF7 在鳞状细胞癌发生中的潜在作用，为潜在有用的预后模式提供了表达特征的见解。
