Data_Sheet_6_Down-Regulation of Collagen Hydroxylation in Colorectal Liver Metastasis.xlsx

Collagen is significantly upregulated in colorectal liver metastasis (CRLM) compared to liver tissue. Expression levels of specific collagen types in CRLM resemble those in colorectal cancer (CRC) and colon tissue. We investigated whether the collagen hydroxylation pattern from the primary tumor also migrates with the metastatic tumor. The degree of collagen alpha-1(I) hydroxylation in colon, CRC, liver, and CRLM tissue of the same individuals (n = 14) was studied with mass spectrometry. The degree of hydroxylation was investigated in 36 collagen alpha-1(I) peptides, covering 54% of the triple helical region. The degree of hydroxylation in liver tissue was similar to that in colon tissue. The overall degree of hydroxylation was significantly lower (9 ± 14%) in CRC tissue and also significantly lower (12 ± 22%) in CRLM tissue compared to colon. Furthermore, eleven peptides with a specific number of hydroxylations are significantly different between CRLM and liver tissue; these peptides could be candidates for the detection of CRLM. For one of these eleven peptides, a matching naturally occurring peptide in urine has been identified as being significantly different between patients suffering from CRLM and healthy controls. The hydroxylation pattern in CRLM resembles partly the pattern in liver, primary colorectal cancer and colon.

相较于肝组织，结直肠癌肝转移（colorectal liver metastasis, CRLM）病灶中的胶原蛋白表达水平显著上调。结直肠癌肝转移灶中特定类型胶原蛋白的表达水平，与结直肠癌（colorectal cancer, CRC）组织及结肠组织的表达水平相似。本研究旨在探究原发肿瘤的胶原蛋白羟化模式是否会随转移性肿瘤一同转移。本研究采用质谱分析法，对14名个体的结肠组织、结直肠癌组织、肝组织及结直肠癌肝转移灶组织中的α1(I)型胶原蛋白羟化程度进行了检测。本次检测覆盖了α1(I)型胶原蛋白的36个肽段，涵盖其三重螺旋区域的54%。肝组织的胶原蛋白羟化程度与结肠组织相近。与结肠组织相比，结直肠癌组织的整体羟化程度显著降低（9 ± 14%），结直肠癌肝转移灶组织的整体羟化程度亦显著降低（12 ± 22%）。此外，11种带有特定羟化修饰数量的肽段在结直肠癌肝转移灶与肝组织之间存在显著差异；这些肽段可作为结直肠癌肝转移检测的潜在候选标志物。在这11种肽段中，有1种对应的天然尿液肽段已被证实，在结直肠癌肝转移患者与健康对照人群之间存在显著差异。结直肠癌肝转移灶的羟化模式，在一定程度上与肝组织、原发结直肠癌组织及结肠组织的羟化模式相似。