Prognostic relevance of collagen XVIII expression in metastatic gastric carcinoma

Abstract

Collagen XVIII is a component of vascular and epithelial basement membranes. The C-terminal fragment of the protein is termed endostatin, and is a potent inhibitor of angiogenesis. No reports on the clinical implications of collagen XVIII expression in human gastric cancer are currently available. Here, we investigate the clinical significance of collagen XVIII expression in gastric cancer. Seven gastric cancer cell lines were subjected to Western blotting. Collagen XVIII expression was examined in 118 gastric carcinoma tissues via immunohistochemistry. Western blotting revealed the presence of the 22-kDa collagen XVIII protein in four of seven gastric cancer cell lines. Immunohistochemistry detected collagen XVIII expression in the tumor cytoplasm in 115 of 118 gastric carcinoma patients (97%). No correlation was evident between collagen XVIII expression score and clinicopathologic findings when all patients were considered together. However, on subgroup analysis, 42 of 70 patients with distant metastasis were classified into low or moderate collagen XVIII expression groups, whereas the remaining 28 patients were grouped as showing high collagen XVIII expression. The prognosis for patients with high collagen XVIII-expressing gastric carcinoma was significantly worse than that for patients displaying low or moderate collagen XVIII expression (median survival time, 7.8 months vs. 18.3 months [log-rank, p = 0.01]; median time to progression, 3 months vs. 8 months [log-rank, p = 0.01]). High expression of collagen XVIII is associated with poor prognosis in patients with metastatic gastric carcinoma. Further studies on larger patient populations are warranted to validate the utility of collagen XVIII as a prognostic biomarker in gastric carcinoma.

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway

“…Most of the 14 genes were closely related to matrix remodeling, which further supported that matrix remodeling is a crucial character of GC progression. Among the 14 genes, most of them have been reported in GC such as the well-known oncogenes PDGFRB 21 , VCAN 22 , and COL18A1 23 , while there were also four genes, MFAP2, OLFML2B, NREP, and COL4A5, that have never been studied in GC. We are especially interested in MFAP2.…”

Proteoglycans as Mediators of Cancer Tissue Mechanics

“…Other pericellular and basal membrane proteoglycans, such as collagen XVIII and collagen XV have also been implicated in cancer progression support, however, limited evidence has been reported on this subject. In metastatic gastric cancer, as well as in non-small cell lung cancer, high expression of collagen XVIII correlated with a poor clinical outcome (Iizasa et al, 2004;Lee et al, 2010). However, both collagen XVIII and XV are integral components of the basal membrane.…”