Valle-Garcia David, Pérez de la Cruz Verónica, Flores Itamar, Salazar Aleli, Pineda Benjamín, Meza-Sosa Karla F
Laboratorio de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez (INNNMVS), Mexico City 14269, Mexico.
Laboratorio de Neurobioquímica y Conducta, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez (INNNMVS), Mexico City 14269, Mexico.
Int J Mol Sci. 2024 Feb 20;25(5):2464. doi: 10.3390/ijms25052464.
Glioblastoma (GB) is the most aggressive and common type of cancer within the central nervous system (CNS). Despite the vast knowledge of its physiopathology and histology, its etiology at the molecular level has not been completely understood. Thus, attaining a cure has not been possible yet and it remains one of the deadliest types of cancer. Usually, GB is diagnosed when some symptoms have already been presented by the patient. This diagnosis is commonly based on a physical exam and imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI), together with or followed by a surgical biopsy. As these diagnostic procedures are very invasive and often result only in the confirmation of GB presence, it is necessary to develop less invasive diagnostic and prognostic tools that lead to earlier treatment to increase GB patients' quality of life. Therefore, blood-based biomarkers (BBBs) represent excellent candidates in this context. microRNAs (miRNAs) are small, non-coding RNAs that have been demonstrated to be very stable in almost all body fluids, including saliva, serum, plasma, urine, cerebrospinal fluid (CFS), semen, and breast milk. In addition, serum-circulating and exosome-contained miRNAs have been successfully used to better classify subtypes of cancer at the molecular level and make better choices regarding the best treatment for specific cases. Moreover, as miRNAs regulate multiple target genes and can also act as tumor suppressors and oncogenes, they are involved in the appearance, progression, and even chemoresistance of most tumors. Thus, in this review, we discuss how dysregulated miRNAs in GB can be used as early diagnosis and prognosis biomarkers as well as molecular markers to subclassify GB cases and provide more personalized treatments, which may have a better response against GB. In addition, we discuss the therapeutic potential of miRNAs, the current challenges to their clinical application, and future directions in the field.
胶质母细胞瘤(GB)是中枢神经系统(CNS)中最具侵袭性和常见的癌症类型。尽管对其生理病理学和组织学有广泛了解,但其分子水平的病因尚未完全清楚。因此,目前仍无法实现治愈,它仍是最致命的癌症类型之一。通常,GB在患者已经出现一些症状时才被诊断出来。这种诊断通常基于体格检查和影像学检查,如计算机断层扫描(CT)和磁共振成像(MRI),并结合或随后进行手术活检。由于这些诊断程序具有很强的侵入性,而且往往只能证实GB的存在,因此有必要开发侵入性较小的诊断和预后工具,以便更早进行治疗,提高GB患者的生活质量。因此,基于血液的生物标志物(BBB)在这种情况下是很好的候选者。微小RNA(miRNA)是小的非编码RNA,已被证明在几乎所有体液中都非常稳定,包括唾液、血清、血浆、尿液、脑脊液(CFS)、精液和母乳。此外,血清中循环的和外泌体中含有的miRNA已成功用于在分子水平上更好地对癌症亚型进行分类,并针对特定病例做出更好的最佳治疗选择。此外,由于miRNA调节多个靶基因,还可作为肿瘤抑制因子和癌基因发挥作用,它们参与了大多数肿瘤的发生、发展,甚至化疗耐药性。因此,在本综述中,我们讨论了GB中失调的miRNA如何用作早期诊断和预后生物标志物以及分子标志物,以对GB病例进行亚分类并提供更个性化的治疗,这可能对GB有更好的反应。此外,我们还讨论了miRNA的治疗潜力、其临床应用目前面临的挑战以及该领域的未来方向。