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文章:

结直肠癌(CRC)细胞增殖的预后生物标志物:从免疫组织化学到分子生物学技术

Prognostic Biomarkers of Cell Proliferation in Colorectal Cancer (CRC): From Immunohistochemistry to Molecular Biology Techniques

原文发布日期:15 September 2023

DOI: 10.3390/cancers15184570

类型: Article

开放获取: 是

 

英文摘要:

Colorectal cancer (CRC) is one of the most common and severe malignancies worldwide. Recent advances in diagnostic methods allow for more accurate identification and detection of several molecular biomarkers associated with this cancer. Nonetheless, non-invasive and effective prognostic and predictive testing in CRC patients remains challenging. Classical prognostic genetic markers comprise mutations in several genes (e.g.,APC,KRAS/BRAF,TGF-β,andTP53). Furthermore, CIN and MSI serve as chromosomal markers, while epigenetic markers include CIMP and many other candidates such asSERP,p14,p16,LINE-1, andRASSF1A. The number of proliferation-related long non-coding RNAs (e.g., SNHG1, SNHG6, MALAT-1, CRNDE) and microRNAs (e.g., miR-20a, miR-21, miR-143, miR-145, miR-181a/b) that could serve as potential CRC markers has also steadily increased in recent years. Among the immunohistochemical (IHC) proliferative markers, the prognostic value regarding the patients’ overall survival (OS) or disease-free survival (DFS) has been confirmed for thymidylate synthase (TS), cyclin B1, cyclin D1, proliferating cell nuclear antigen (PCNA), and Ki-67. In most cases, the overexpression of these markers in tissues was related to worse OS and DFS. However, slowly proliferating cells should also be considered in CRC therapy (especially radiotherapy) as they could represent a reservoir from which cells are recruited to replenish the rapidly proliferating population in response to cell-damaging factors. Considering the above, the aim of this article is to review the most common proliferative markers assessed using various methods including IHC and selected molecular biology techniques (e.g., qRT-PCR, in situ hybridization, RNA/DNA sequencing, next-generation sequencing) as prognostic and predictive markers in CRC.

 

摘要翻译: 

结直肠癌是全球范围内最常见且最严重的恶性肿瘤之一。近年来诊断方法的进步使得与这种癌症相关的多种分子生物标志物能够被更精确地识别和检测。然而,对结直肠癌患者进行无创且有效的预后和预测检测仍然面临挑战。经典的预后遗传标志物包括多个基因的突变(如APC、KRAS/BRAF、TGF-β和TP53)。此外,染色体不稳定性(CIN)和微卫星不稳定性(MSI)可作为染色体标志物,而表观遗传标志物则包括CpG岛甲基化表型(CIMP)及其他多种候选标志物,如SERP、p14、p16、LINE-1和RASSF1A。近年来,可作为潜在结直肠癌标志物的增殖相关长链非编码RNA(如SNHG1、SNHG6、MALAT-1、CRNDE)和微小RNA(如miR-20a、miR-21、miR-143、miR-145、miR-181a/b)的数量也在稳步增加。在免疫组织化学(IHC)增殖标志物中,胸苷酸合成酶(TS)、细胞周期蛋白B1、细胞周期蛋白D1、增殖细胞核抗原(PCNA)和Ki-67对患者总生存期(OS)或无病生存期(DFS)的预后价值已得到证实。在大多数情况下,这些标志物在组织中的过度表达与较差的OS和DFS相关。然而,在结直肠癌治疗(尤其是放疗)中也应考虑缓慢增殖的细胞,因为它们可能构成一个细胞库,在细胞损伤因素作用下,这些细胞会被招募以补充快速增殖的细胞群。综上所述,本文旨在综述通过免疫组织化学及选定的分子生物学技术(如qRT-PCR、原位杂交、RNA/DNA测序、下一代测序)评估的最常见增殖标志物,作为结直肠癌的预后和预测标志物。

 

原文链接:

Prognostic Biomarkers of Cell Proliferation in Colorectal Cancer (CRC): From Immunohistochemistry to Molecular Biology Techniques

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