Abstract

Breast cancer is the most common cancer in women. Despite advances in screening women for genetic predisposition to breast cancer and risk stratification, a majority of women carriers remain undetected until they become affected. Thus, there is a need to develop a cost-effective, rapid, sensitive and non-invasive early-stage diagnostic method. Kinases are involved in all fundamental cellular processes and mutations in kinases have been reported as drivers of cancer. PPARγ is a ligand-activated transcription factor that plays important roles in cell proliferation and metabolism. However, the complete set of kinases modulated by PPARγ is still unknown. In this study, we identified human kinases that are potential PPARγ targets and evaluated their differential expression and gene pair correlations in human breast cancer patient dataset TCGA-BRCA. We further confirmed the findings in human breast cancer cell lines MCF7 and SK-BR-3 using a kinome array. We observed that gene pair correlations are lost in tumours as compared to healthy controls and could be used as a supplement strategy for diagnosis and prognosis of breast cancer.

摘要

乳腺癌是女性最常见的癌症。尽管在筛查女性乳腺癌遗传易感性和风险分层方面取得了进展，但大多数女性携带者在受到影响之前仍未被发现。因此，需要开发一种具有成本效益、快速、灵敏和无创的早期诊断方法。激酶参与所有基本的细胞过程，据报道激酶的突变是癌症的驱动因素。PPARγ是一种配体激活的转录因子，在细胞增殖和代谢中起重要作用。然而，由 PPARγ 调节的完整激酶组仍然未知。在这项研究中，我们鉴定了作为潜在 PPARγ 靶标的人类激酶，并评估了它们在人类乳腺癌患者数据集 TCGA-BRCA 中的差异表达和基因对相关性。我们使用激酶组阵列进一步证实了在人乳腺癌细胞系 MCF7 和 SK-BR-3 中的发现。我们观察到，与健康对照相比，肿瘤中的基因对相关性丢失，可用作乳腺癌诊断和预后的补充策略。