Fayazfar Setareh, Zali Hakimeh, Arefi Oskouie Afsaneh, Asadzadeh Aghdaei Hamid, Rezaei Tavirani Mostafa, Nazemalhosseini Mojarad Ehsan
Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gastroenterol Hepatol Bed Bench. 2019 Fall;12(4):328-339.
This paper aimed to identify new candidate biomarkers in blood for early diagnosis of CRC.
Colorectal cancer (CRC) is the third most widespread malignancies increasing globally. The high mortality rate associated with colorectal cancer is due to the delayed diagnosis in an advanced stage while the metastasis has occurred. For better clinical management and subsequently to reduce mortality of CRC, early detection biomarkers are in high demand.
A 2D-PAGE separation of proteins was performed followed by tandem mass Spectrometry (MALDI-TOF-TOF) to discover potential plasma protein markers for CRC and AA (advanced adenomas). Furthermore, western blot method was used to confirm a part of the results in colorectal tissue samples.
The significantly altered proteins including HPR, HP, ALB, KRT1, APOA1, FGB, IGJ and C4A were down-regulated in polyp relative to normal, and CRC compare to polyp surprisingly, and inversely, ORM2 was up-regulated with the fold change ≥ 2 and p-value ≤ 0.05. We also surveyed APOA1, FGB, and C4A for further confirmation of their expression changes by western blotting. All three of them showed a decreasing trend from normal toward CRC tissue samples as it mentioned before, but just changes of FGB and C4A were significant.
The results demonstrated that plasma proteins can be less invasive markers for the detection of CRC. FGB and C4A can be considered as plasma potential biomarkers to early diagnosis of CRC patients and understanding the underlying procedures in tumorigenesis. Undoubtedly, the additional study must be conducted on large scale cohorts to verify the results.
本文旨在鉴定血液中用于结直肠癌早期诊断的新候选生物标志物。
结直肠癌（CRC）是全球范围内第三大广泛传播的恶性肿瘤。与结直肠癌相关的高死亡率是由于在晚期发生转移时诊断延迟所致。为了更好地进行临床管理并随后降低结直肠癌的死亡率，对早期检测生物标志物的需求很高。
进行蛋白质的二维聚丙烯酰胺凝胶电泳分离，随后进行串联质谱分析（基质辅助激光解吸电离飞行时间质谱），以发现结直肠癌和高级别腺瘤（AA）的潜在血浆蛋白标志物。此外，采用蛋白质印迹法在结直肠组织样本中对部分结果进行验证。
与正常组织相比，息肉中显著改变的蛋白质包括结合珠蛋白（HPR）、触珠蛋白（HP）、白蛋白（ALB）、角蛋白1（KRT1）、载脂蛋白A1（APOA1）、纤维蛋白原（FGB）、免疫球蛋白J链（IGJ）和补体C4A均下调，而与息肉相比，结直肠癌中这些蛋白更是惊人地下调，相反，ORM2上调，倍数变化≥2且p值≤0.05。我们还通过蛋白质印迹法对APOA1、FGB和C4A的表达变化进行进一步验证。正如之前所提到的，这三种蛋白从正常组织到结直肠癌组织样本均呈下降趋势，但只有FGB和C4A的变化具有统计学意义。
结果表明，血浆蛋白可作为检测结直肠癌的侵入性较小的标志物。FGB和C4A可被视为结直肠癌患者早期诊断及了解肿瘤发生潜在过程的血浆潜在生物标志物。毫无疑问，必须在大规模队列中进行进一步研究以验证这些结果。
