Dolatabadi Behnaz, Peymani Maryam, Rouhi Leila, Salehzadeh Ali, Hushmandi Kiavash, Hashemi Mehrdad
Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
Mol Cell Probes. 2024 Dec;78:101985. doi: 10.1016/j.mcp.2024.101985. Epub 2024 Oct 8.
Various pieces of evidence suggest an elevation in the levels of EGFR and HER2 in different cancers leading to the proliferation, invasion, and metastasis of cancer cells. In this study, we conducted a comprehensive investigation into the expression alterations of these two receptors in various cancers using in silico data. In addition, we investigated the therapeutic potential of lapatinib as an inhibitor of these receptors in various cancer types.
RNAseq data for prevalent cancers were downloaded from The Cancer Genome Atlas (TCGA). After initial preprocessing, expression changes of HER2, EGFR, and candidate genes-identified based on their association with EGFR and HER2 signaling pathways-were examined. Human protein atlas data were utilized to assess the protein expression of HER2 and EGFR. GSE129254 was employed to identify molecular pathways and candidate genes associated with lapatinib. The protein-protein interaction network was used to identify lapatinib-influenced hub genes. Clinical data for common cancers were used to investigate the correlation between the expression of candidate genes and patients' mortality rates by Cox regression test.
The findings clearly indicated a significant increase in the expression levels of HER2 and EGFR in cancers such as kidney, lung, breast, bladder, pancreas, head and neck, stomach, and endometrial, both at the mRNA and protein levels (p-value <0.01). Additionally, more than 30 % of samples in some cancers showed a twofold increase in HER2 or EGFR expression. The analysis of GSE129254 data revealed that lapatinib reduces the expression of numerous genes associated with cell proliferation. METTL1, LYAR, LTV1, CCND1, NOP2, and DDX21 were identified as hub genes related to the effect of lapatinib. Our results demonstrated that many hub genes exhibited elevated expression in candidate cancers, and the upregulation of some of them was correlated with poor prognosis.
Our results indicate an upregulation in the expression levels of HER2 and EGFR in certain common cancers, suggesting that lapatinib, in addition to breast cancer, could be considered for the treatment of these cancers. Furthermore, we demonstrated that some genes with increased expression in prevalent cancers and associated with poor prognosis have the potential to be modulated by lapatinib.
多项证据表明，不同癌症中表皮生长因子受体（EGFR）和人表皮生长因子受体2（HER2）水平升高，导致癌细胞增殖、侵袭和转移。在本研究中，我们利用计算机模拟数据，对这两种受体在各种癌症中的表达变化进行了全面调查。此外，我们还研究了拉帕替尼作为这些受体抑制剂在各种癌症类型中的治疗潜力。
从癌症基因组图谱（TCGA）下载常见癌症的RNA测序数据。经过初步预处理后，检测HER2、EGFR以及根据其与EGFR和HER2信号通路的关联确定的候选基因的表达变化。利用人类蛋白质图谱数据评估HER2和EGFR的蛋白质表达。采用GSE129254来鉴定与拉帕替尼相关的分子途径和候选基因。蛋白质-蛋白质相互作用网络用于鉴定受拉帕替尼影响的枢纽基因。通过Cox回归检验，使用常见癌症的临床数据来研究候选基因表达与患者死亡率之间的相关性。
研究结果清楚地表明，在肾脏、肺、乳腺、膀胱、胰腺、头颈部、胃和子宫内膜等癌症中，HER2和EGFR的mRNA和蛋白质水平均显著升高（p值<0.01）。此外，某些癌症中超过30%的样本显示HER2或EGFR表达增加了两倍。对GSE129254数据的分析表明，拉帕替尼可降低许多与细胞增殖相关基因的表达。METTL1、LYAR、LTV1、CCND1、NOP2和DDX21被鉴定为与拉帕替尼作用相关的枢纽基因。我们的结果表明，许多枢纽基因在候选癌症中表达升高，其中一些基因的上调与预后不良相关。
我们的结果表明，某些常见癌症中HER2和EGFR的表达水平上调，这表明除乳腺癌外，拉帕替尼也可考虑用于治疗这些癌症。此外，我们证明，在常见癌症中表达增加且与预后不良相关的一些基因有可能被拉帕替尼调节。
