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接受化疗和贝伐珠单抗治疗的转移性结直肠癌患者血液纤维化生物标志物的预后价值。

Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab.

机构信息

Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.

Biomarkers and Research, Nordic Bioscience, Herlev Hovedgade 205-207, 2730, Herlev, Denmark.

出版信息

Sci Rep. 2021 Jan 13;11(1):865. doi: 10.1038/s41598-020-79608-0.

DOI:10.1038/s41598-020-79608-0
PMID:33441622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7806753/
Abstract

A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54-2.63; PRO-C6: HR = 1.6, 95%CI = 1.24-2.11; C6M: HR = 1.4, 95%CI = 1.05-1.78; C6Mα3: HR = 1.6, 95%CI = 1.16-2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03-0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30-5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.

摘要

富含型结直肠癌细胞外基质，其特征为癌症相关成纤维细胞衍生的 III 型和 VI 型胶原过度更新，可导致药物摄取减少和治疗反应不良。我们研究了 III 型和 VI 型胶原生物标志物与转移性结直肠癌（mCRC）患者总生存期（OS）之间的关系。在接受贝伐单抗和化疗治疗前，收集了 252 例 mCRC 患者的血清样本。通过 ELISA 测定反映 III 型胶原形成（PRO-C3）和 VI 型胶原（PRO-C6）以及 VI 型胶原降解（C6M 和 C6Mα3）的生物标志物的血清浓度。单独、联合以及在调整癌胚抗原（CEA）、乳酸脱氢酶（LDH）和体能状态（PS）后，评估这些生物标志物与 OS 的相关性。各胶原生物标志物基线水平（>中位数）较高与 OS 较短显著相关（PRO-C3：HR=2.0，95%CI=1.54-2.63；PRO-C6：HR=1.6，95%CI=1.24-2.11；C6M：HR=1.4，95%CI=1.05-1.78；C6Mα3：HR=1.6，95%CI=1.16-2.07）。在调整 CEA、LDH 和 PS 后，PRO-C3 和 PRO-C6 仍具有统计学意义。各胶原生物标志物之间相关性较弱（r=0.03-0.59），联合所有标志物可提高预测能力（HR=3.6，95%CI=2.30-5.76）。胶原生物标志物可预测 mCRC 患者的 OS 较短。这支持胶原和 CAF 生物学在 CRC 中很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/b63fdf23896e/41598_2020_79608_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/d19c270be3c1/41598_2020_79608_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/e2a24ac54a13/41598_2020_79608_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/0505492357d3/41598_2020_79608_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/b8dfbf2fe965/41598_2020_79608_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/b63fdf23896e/41598_2020_79608_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/d19c270be3c1/41598_2020_79608_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/e2a24ac54a13/41598_2020_79608_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/0505492357d3/41598_2020_79608_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/b8dfbf2fe965/41598_2020_79608_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b0/7806753/b63fdf23896e/41598_2020_79608_Fig5_HTML.jpg

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