Department of Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510000, P.R. China.
Department of Anorectal Surgery, Zhongshan Hospital Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, Guangdong 528400, P.R. China.
Oncol Rep. 2020 Oct;44(4):1671-1685. doi: 10.3892/or.2020.7729. Epub 2020 Aug 11.
As the major component of the tumor matrix, collagen greatly influences tumor invasion and prognosis. The present study compared the remodeling of collagen and collagenase in 56 patients with colorectal cancer (CRC) using Sirius red stain and immunohistochemistry, exploring the relationship between collagen remodeling and the prognosis of CRC. Weak or strong changes in collagen fiber arrangement in birefringence were observed. With the exception of a higher density, weak changes equated to a similar arrangement in normal collagen, while strong changes facilitated cross‑linking into bundles. Compared with normal tissues, collagen I (COL I) and III (COL III) deposition was significantly increased in CRC tissues, and was positively correlated with the metastasis status. In tissues without distant metastasis, collagen IV (COL IV) levels were higher than that in normal tissues, while in tissues with distant metastasis, collagen IV expression was significantly lower. Furthermore, the expression of matrix metalloproteinase (MMP)‑1, MMP‑2, MMP‑7, MMP‑9 and lysyl oxidase‑like 2 (LOXL2) was found to be elevated in the cancer stroma, which contributed to the hyperactive remodeling of collagen. The association between collagen‑related genes and the occurrence and prognosis of CRC were analyzed using biometric databases. The results indicated that patients with upregulated expression of a combination of coding genes for collagen and collagenase exhibited poorer overall survival times. The coding genes COL1A1‑2, COL3A1, COL4A3, COL4A6 and MMP2 may therefore be used as biomarkers to predict the prognosis of patients with CRC. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggest that collagen may promote tumor development by activating platelets. Collectively, the abnormal collagen remodeling, including associated protein and coding genes is associated with the tumorigenesis and metastasis, affecting the prognosis of patients with CRC.
作为肿瘤基质的主要成分，胶原蛋白极大地影响肿瘤的侵袭和预后。本研究采用天狼猩红染色和免疫组织化学方法比较了 56 例结直肠癌（CRC）患者的胶原蛋白和胶原酶重塑，探讨了胶原蛋白重塑与 CRC 预后的关系。观察到双折射中胶原纤维排列的弱或强变化。除了密度较高外，弱变化等同于正常胶原蛋白的相似排列，而强变化则有利于交联成束。与正常组织相比，CRC 组织中 COL I 和 COL III 的沉积明显增加，并且与转移状态呈正相关。在无远处转移的组织中，COL IV 水平高于正常组织，而在有远处转移的组织中，COL IV 的表达显著降低。此外，在癌基质中发现基质金属蛋白酶（MMP）-1、MMP-2、MMP-7、MMP-9 和赖氨酰氧化酶样 2（LOXL2）的表达升高，这有助于胶原的过度活跃重塑。使用生物计量数据库分析了与胶原相关的基因与 CRC 的发生和预后的关系。结果表明，表达上调的编码胶原和胶原酶的组合的患者总生存时间更差。因此，COL1A1-2、COL3A1、COL4A3、COL4A6 和 MMP2 等编码基因可作为预测 CRC 患者预后的标志物。此外，基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析的结果表明，胶原蛋白可能通过激活血小板促进肿瘤的发展。综上所述，异常的胶原蛋白重塑，包括相关蛋白和编码基因，与肿瘤的发生和转移有关，影响 CRC 患者的预后。
