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根据肿瘤分期和部位对结直肠癌进行 N-糖基化组学分析。

N-glycomic profiling of colorectal cancer according to tumor stage and location.

机构信息

Department of Surgery, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Department of Pathology, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

出版信息

PLoS One. 2020 Jun 29;15(6):e0234989. doi: 10.1371/journal.pone.0234989. eCollection 2020.

Abstract

Alterations in glycosylation are seen in many types of cancer, including colorectal cancer (CRC). Glycans, the sugar moieties of glycoconjugates, are involved in many important functions relevant to cancer and can be of value as biomarkers. In this study, we have used mass spectrometry to analyze the N-glycan profiles of 35 CRC tissue samples and 10 healthy tissue samples from non-CRC patients who underwent operations for other reasons. The tumor samples were divided into groups depending on tumor location (right or left colon) and stage (II or III), while the healthy samples were divided into right or left colon. The levels of neutral and acidic N-glycan compositions and glycan classes were analyzed in a total of ten different groups. Surprisingly, there were no significant differences in glycan levels when all right- and left-sided CRC samples were compared, and few differences (such as in the abundance of the neutral N-glycan H3N5) were seen when the samples were divided according to both location and stage. Multiple significant differences were found in the levels of glycans and glycan classes when stage II and III samples were compared, and these glycans could be of value as candidates for new markers of cancer progression. In order to validate our findings, we analyzed healthy tissue samples from the right and left colon and found no significant differences in the levels of any of the glycans analyzed, confirming that our findings when comparing CRC samples from the right and left colon are not due to normal variations in the levels of glycans between the healthy right and left colon. Additionally, the levels of the acidic glycans H4N3F1P1, H5N4F1P1, and S1H5N4F1 were found to change in a cancer-specific but colon location-nonspecific manner, indicating that CRC affects glycan levels in similar ways regardless of tumor location.

摘要

糖基化的改变在许多类型的癌症中都有出现,包括结直肠癌(CRC)。糖链是糖缀合物的糖部分,参与许多与癌症相关的重要功能,并且可以作为生物标志物具有价值。在这项研究中,我们使用质谱分析了 35 个 CRC 组织样本和 10 个来自非 CRC 患者的健康组织样本的 N-糖基化谱,这些患者因其他原因接受手术。根据肿瘤位置(右结肠或左结肠)和分期(II 期或 III 期)将肿瘤样本分为不同组,而健康样本则分为右结肠或左结肠。总共分析了十个不同组的中性和酸性 N-糖基化组成和糖基类别的水平。令人惊讶的是,当所有右和左结肠癌样本进行比较时,糖基水平没有明显差异,当根据位置和分期对样本进行划分时,只有少数差异(如中性 N-糖基化 H3N5 的丰度)。当比较 II 期和 III 期样本时,发现糖基和糖基类别的水平存在多个显著差异,这些糖基可能是癌症进展新标志物的候选物。为了验证我们的发现,我们分析了来自右结肠和左结肠的健康组织样本,发现任何分析的糖基水平均无显著差异,证实了我们在比较右和左结肠癌 CRC 样本时的发现不是由于健康右结肠和左结肠之间糖基水平的正常变化所致。此外,还发现酸性糖基 H4N3F1P1、H5N4F1P1 和 S1H5N4F1 的水平以癌症特异性但结肠位置非特异性的方式发生变化,表明 CRC 以相似的方式影响糖基水平,而与肿瘤位置无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc3c/7323945/c85f04757684/pone.0234989.g001.jpg

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