Fellizar Allan, Refuerzo Vivencio, Ramos John Donnie, Albano Pia Marie
The Graduate School, University of Santo Tomas, Manila, Philippines.
Department of Pathology and Laboratories, Mariano Marcos Memorial Hospital and Medical Center, Batac, Philippines.
J Pathol Transl Med. 2023 May;57(3):147-157. doi: 10.4132/jptm.2022.02.19. Epub 2022 May 3.
MicroRNAs (miRNA/miR) play significant roles in the regulation of cell differentiation, cell cycle progression, and apoptosis. They become dysregulated during carcinogenesis and are eventually released into the circulation, enabling their detection in body fluids. Thus, this study compared the miRNA expression in tissue and plasma samples of colorectal cancer (CRC) patients and clinically healthy controls and determined miRNA expression as a potential CRC biomarker.
Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), miR-21-5p, miR-29a-3p, miR-92a-3p, miR-135b-5p, miR-196b-5p, and miR-197-3p, expression was analyzed and compared between the malignant (n = 41) and the adjacent neoplasm free mucosal tissues (n = 41) of CRC patients. The findings were validated in plasma samples (n = 36) collected from the same CRC patients prior to surgery or any form of treatment and compared to plasma from their age and sex-matched controls (n = 36).
MiR-21-5p, miR-29a-3p, miR-92a-3p, and miR- 196b-5p were upregulated and miR-135b-5p was downregulated in CRC malignant tissues compared to their expression in adjacent neoplasm-free tissue. This was further observed in the plasma of the same CRC cases compared to controls. MiR-92a-3p showed itself the most sensitive (0.93; p < .001) and most specific (0.95; p < .001) in detecting CRC in tissue. In plasma, miR-196b-5p was the most sensitive (0.97; p < .001) and specific (0.94; p < .001) in detecting CRC. Plasma miR-92a-3p and miR-196b-5p were the most sensitive (0.95; p < .001) and specific (0.94; p < .001) in the early detection of CRC.
Results show that specific miRNAs dysregulated in malignant tissues are released and can be detected in the circulation, supporting their potential as non-invasive biomarkers of CRC.
微小RNA（miRNA/miR）在细胞分化、细胞周期进程和细胞凋亡的调控中发挥着重要作用。它们在致癌过程中失调，并最终释放到循环系统中，从而能够在体液中被检测到。因此，本研究比较了结直肠癌（CRC）患者与临床健康对照者的组织和血浆样本中的miRNA表达情况，并确定miRNA表达作为潜在的CRC生物标志物。
使用定量逆转录聚合酶链反应（RT-qPCR）分析并比较了CRC患者的恶性组织（n = 41）和相邻无肿瘤黏膜组织（n = 41）中miR-21-5p、miR-29a-3p、miR-92a-3p、miR-135b-5p、miR-196b-5p和miR-197-3p的表达。在同一CRC患者手术或任何形式治疗前采集的血浆样本（n = 36）中验证了这些发现，并与年龄和性别匹配的对照者的血浆（n = 36）进行了比较。
与相邻无肿瘤组织中的表达相比，miR-21-5p、miR-29a-3p、miR-92a-3p和miR-196b-5p在CRC恶性组织中上调，而miR-135b-5p下调。在同一CRC病例的血浆与对照者的血浆中进一步观察到了这一现象。miR-92a-3p在检测组织中的CRC时表现出最高的敏感性（0.93；p <.001）和特异性（0.95；p <.001）。在血浆中，miR-196b-5p在检测CRC时最敏感（0.97；p <.001）且特异性最强（0.94；p <.001）。血浆miR-92a-3p和miR-196b-5p在CRC的早期检测中最敏感（0.95；p <.001）且特异性最强（0.94；p <.001）。
结果表明，在恶性组织中失调的特定miRNA会释放到循环系统中并能够被检测到，这支持了它们作为CRC非侵入性生物标志物的潜力。
