由于缺乏ER的表达,三阴性乳腺癌(TNBC)的治疗与挑战有关。PR,和肿瘤细胞中的HER2受体。本研究旨在鉴定在TNBC中具有潜在治疗靶标的基因。下载关于乳腺癌(BC)的癌症基因组图谱的数据。经过初始预处理,癌症样本分为四组:TNBC,HER2阳性,管腔A,计算了这些组间的基因表达差异,集中在TNBC中显示差异表达的基因。进行蛋白质-蛋白质相互作用网络以在与TNBC相关的候选基因中鉴定hub基因。使用来自人蛋白质图谱的免疫组织化学数据评估候选基因的蛋白质表达。使用来自PharmacoDB的数据鉴定与hub基因相关的耐药性和敏感性。使用TNBC样品和RT-qPCR方法确认结果。我们的发现揭示了八个基因,即PLK1,KIF4A,CDCA5,UBE2C,CDT1,SKA3,AURKB,与其他亚组相比,TNBC亚组中的PTTG1和PTTG1在RNA水平上有显着上调,可以认为是TNBC中的hub基因。与其他亚组相比,它们在TNBC样本中的表达水平具有较高的敏感性和特异性.RT-qPCR结果还表明,与健康组织和其他亚组相比,TNBC中SKA3和PTTG1的水平显著增加。这些基因的蛋白质表达在一些BC样品中显著高。PharmacoDB数据显示,一些候选基因与GSK461364和IKK16的药物敏感性密切相关。本研究结果显示PLK1、KIF4A、CDCA5,UBE2C,CDT1,SKA3,AURKB,与其他BC亚组相比,TNBC中的PTTG1。这些基因显示出作为TNBC亚组的治疗靶标的相当大的希望。
The treatment of triple-negative breast cancer (TNBC) has been associated with challenges due to the lack of expression of ER, PR, and HER2 receptors in tumor cells. This study aimed to identify genes with potential therapeutic targets in TNBC. Data from the cancer genome atlas regarding breast cancer (BC) were downloaded. After initial preprocessing, cancer samples were categorized into four groups: TNBC, HER2-positive, luminal A, and luminal B. Gene expression differences between these groups were calculated, focusing on genes that showed differential expression in TNBC. A protein-protein interaction network was conducted to identify hub genes among the candidate genes related to TNBC. The protein expression of candidate genes was assessed using immunohistochemistry data from the human protein atlas. Drug resistance and sensitivity associated with hub genes were identified using data from PharmacoDB. TNBC samples and the RT-qPCR method were used to confirm the results. Our findings revealed that eight genes, namely PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1, had significant upregulation at the RNA level in TNBC subgroup compared to other subgroups and could be considered hub genes in TNBC. Compared to other subgroups, their expression level in TNBC samples had high sensitivity and specificity. RT-qPCR results also demonstrated a significant increase in levels of SKA3 and PTTG1 in the TNBC compared to healthy tissue and other subgroups. The protein expression of these genes was notably high in some BC samples. PharmacoDB data showed that some candidate genes were closely linked to drug sensitivity of GSK 461364 and IKK 16. The results of this study showed a significant increase in the expression level of PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1 in TNBC compared to other BC subgroups. These genes show considerable promise as therapeutic targets for the TNBC subgroup.