Jeleń Agnieszka, Żebrowska-Nawrocka Marta, Łochowski Mariusz, Szmajda-Krygier Dagmara, Balcerczak Ewa
Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
Laboratory of Molecular Diagnostics, BRaIn Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland.
Biomedicines. 2024 Oct 19;12(10):2394. doi: 10.3390/biomedicines12102394.
ATP-binding cassette subfamily G member 2 [ABCG2/breast cancer resistance protein (BCRP)] contributes to mechanisms of multidrug resistance (MDR) and is a marker of side population (SP) cells in human cancers. The primary objective of this study was to investigate the impact of gene expression on the non-small cell lung cancer (NSCLC) development, course of cancer disease, and patient prognosis using publicly available data. Obtained results were supplemented with assessment of expression in blood of NSCLC patients. The dataset of lung cancer was analyzed utilizing the TIMER 2.0, UALCAN, TNMplot, MEXPRESS, cBioPortal, MethSurv, KM Plotter, STRING, and ShinyGO 0.80 databases. Blood samples from 50 patients were assessed using the real-time PCR method. The gene was expressed at a low level in NSCLC, and did not correlate with clinical aggressiveness of lung cancer. Higher expression improved overall survival, but only in LUAD. In addition, CpG sites located on the CpG island affecting the NSCLC patient's prognosis were indicated. In the case of our own laboratory results, the study did not reveal any changes in the expression levels in blood collected from patients at different time points during the diagnostic-therapeutic procedure. In the in silico analysis, most ABCG2 protein interactors were associated with the development of drug resistance. ABCG2 appears to have a particularly significant impact on the survival of patients with lung cancer and on the effect of immunotherapy related to immune cell infiltration. Presented findings may support personalized medicine strategies based on bioinformatics findings.
ATP结合盒亚家族G成员2[ABCG2/乳腺癌耐药蛋白(BCRP)]参与多药耐药(MDR)机制,是人类癌症中侧群(SP)细胞的标志物。本研究的主要目的是利用公开可用数据研究该基因表达对非小细胞肺癌(NSCLC)发展、癌症病程和患者预后的影响。通过评估NSCLC患者血液中的该基因表达来补充所得结果。利用TIMER 2.0、UALCAN、TNMplot、MEXPRESS、cBioPortal、MethSurv、KM Plotter、STRING和ShinyGO 0.80数据库分析肺癌数据集。使用实时PCR方法评估50例患者的血样。该基因在NSCLC中低表达,与肺癌的临床侵袭性无关。较高的该基因表达改善了总生存期,但仅在肺腺癌(LUAD)中如此。此外,还指出了位于影响NSCLC患者预后的CpG岛上的CpG位点。就我们自己的实验室结果而言,该研究未发现诊断治疗过程中不同时间点采集的患者血液中该基因表达水平有任何变化。在计算机分析中,大多数ABCG2蛋白相互作用分子与耐药性的发展有关。ABCG2似乎对肺癌患者的生存以及与免疫细胞浸润相关的免疫治疗效果具有特别显著的影响。所呈现的研究结果可能支持基于生物信息学研究结果的个性化医疗策略。