Prognostic significance of abnormal matrix collagen remodeling in colorectal cancer based on histologic and bioinformatics analysis

Abstract

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.

Extracellular vesicle molecular signatures characterize metastatic dynamicity in ovarian cancer

“…The extracellular matrix (ECM) is a key component of the TME, and undergoes remodeling during many of the stages of metastasis establishment (63)(64)(65). This remodeling plays a key role particularly in the development and progression of many epithelial cancers including ovarian cancer (33,34,(66)(67)(68). Our 10-gene signature, which overlaps with the signature elucidated by Cheon et al, was thus focused on collagen remodeling genes that are implicated in invasion and metastases in cancer (34,67,68).…”

“…(28) have a common functional goal of altering the tumor microenvironment (TME) through collagen remodeling. Collagen remodeling is a key event in metastasis and correlates with poor prognosis in multiple cancers (33). Collagen remodeling in ovarian cancer is thought to not only contribute to peritoneal metastases and ascites formation (28) but also to platinum drug resistance (34).…”

Alcohol Intake and Alcohol–SNP Interactions Associated with Prostate Cancer Aggressiveness

“…In addition, binge alcohol intake could induce SYK activation in an animal study [ 74 ], and SYK was associated with the development of alcoholic liver disease and liver fibrosis [ 75 ]. In addition, expression of COL4A3 was associated with tumor size, higher grade, metastasis, and invasion in several malignancies [ 76 , 77 , 78 ].…”

Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties

“…The organisation of collagen network has been demonstrated to predict metastases [ 34 ]. Liang Y et al reported that collagen arrangements with strong changes in collagen fibres affects the metastatic potential of CRC [ 35 ]. In this study we have identified a collagen network within the mesenteric pAT.…”