Hamfjord Julian, Saldova Radka, Stöckmann Henning, Sandhu Vandana, Bowitz Lothe Inger Marie, Buanes Trond, Lingjærde Ole Christian, Labori Knut Jørgen, Rudd Pauline M, Kure Elin H
NIBRT GlycoScience Group, The National Institute for Bioprocessing Research and Training , Dublin, Ireland.
Department of Environmental and Health Studies, Faculty of Arts and Sciences, Telemark University College , 3800 Bo in Telemark, Norway.
J Proteome Res. 2015 Dec 4;14(12):5144-56. doi: 10.1021/acs.jproteome.5b00395. Epub 2015 Nov 17.
Serum N-glycans are promising biomarkers for systemic disease states. Better understanding of the serum N-glycome of patients with resectable periampullary adenocarcinoma may identify novel prognostic markers for this disease. Serum N-glycans in 70 patients with resectable periampullary adenocarcinoma, 15 patients with benign periampullary tumor, and 129 healthy individuals were quantified using ultra performance liquid chromatography. High-sensitivity C-reactive protein (hsCRP) was analyzed for all samples using an immunoturbidimetric method. The N-glycome was compared to clinical and histopathological data, and to the acute phase response as measured by hsCRP. Whole-genome tumor tissue mRNA expression data were used for correlation and enrichment analysis to investigate underlying biological processes giving rise to changes in the serum N-glycome. Significant changes were found in the serum N-glycome of patients with periampullary adenocarcinoma (n = 70) compared to healthy individuals (n = 129). No significant differences were found between patients with benign (n = 15) and malignant periampullary tumors (n = 70). Many alterations in the N-glycome correlated with systemic acute phase response as measured by hsCRP. Enrichment analysis indicated that immunologic pathways of the cancer microenvironment correlate with specific features of the serum N-glycome. Certain glycans were associated with poor overall and disease free survival in patients with pancreatobiliary type of periampullary adenocarcinoma. Our study supports the hypothesis that certain factors secreted by the tumor affect liver and plasma cells to orchestrate the changes in the serum N-glycome observed. The serum N-glycome could potentially reflect modified phenotypes of the host and/or tumor microenvironment. The prognostic impact of the serum N-glycome should be evaluated in larger, prospective studies.
血清N-聚糖是全身性疾病状态很有前景的生物标志物。更好地了解可切除壶腹周围腺癌患者的血清N-糖组可能会为该疾病确定新的预后标志物。使用超高效液相色谱法对70例可切除壶腹周围腺癌患者、15例壶腹周围良性肿瘤患者和129名健康个体的血清N-聚糖进行了定量分析。使用免疫比浊法对所有样本分析高敏C反应蛋白（hsCRP）。将N-糖组与临床和组织病理学数据以及hsCRP所测量的急性期反应进行比较。利用全基因组肿瘤组织mRNA表达数据进行相关性和富集分析，以研究导致血清N-糖组变化的潜在生物学过程。与健康个体（n = 129）相比，壶腹周围腺癌患者（n = 70）的血清N-糖组有显著变化。壶腹周围良性肿瘤患者（n = 15）和恶性肿瘤患者（n = 70）之间未发现显著差异。N-糖组的许多改变与hsCRP所测量的全身性急性期反应相关。富集分析表明，癌症微环境的免疫途径与血清N-糖组的特定特征相关。某些聚糖与胰胆管型壶腹周围腺癌患者的总生存期和无病生存期较差有关。我们的研究支持这样的假设，即肿瘤分泌的某些因子影响肝脏和浆细胞，从而协调观察到的血清N-糖组变化。血清N-糖组可能潜在反映宿主和/或肿瘤微环境的改变表型。血清N-糖组的预后影响应在更大规模的前瞻性研究中进行评估。
