CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

Abstract

Abstract. The aim of this study was to examine the expression of CD44v6, CD54, Cdx2, CXCL5, Cyclin B1, MMP-7, nm23, RCAS1 and Survivin in primary gastric cancer and to investigate whether these molecules were useful in predicting the lymph node status. They were selected as candidates for indicators of lymph node metastasis from various kinds of cancer-associated genes reported previously. In 135 cases of radically resected primary gastric adenocarcinoma, we investigated the association between the expression of these molecules and clinocopathologic factors by immunohistochemistry. The results revealed that the expression of CD44v6 and MMP-7 were significantly associated with lymph node status. By contrast, nuclear Cdx2 expression was found to be inversely correlated with lymph node metastasis. Moreover, multivariate analysis demonstrated that CD44v6, MMP-7 and nuclear Cdx2 were independent predictors for lymph node status. In conclusion, our results suggest that positive expression of both CD44v6 and MMP-7, and negative expression of nuclear Cdx2 may serve as powerful predictors of lymph node metastasis in gastric cancer. Combined evaluation of these markers could be further useful to predict lymph node status clinically.

Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer

“…Okayama et al proved that MMP-7, among others, was a significant biomarker for prediction of lymph node metastasis in primary gastric cancer. It was also strongly correlated with depth of invasion and stage of the disease [72]. Similar results were presented in the research of Yamashita et al-MMP-7 levels were higher in gastric cancer with vascular invasion compared to a group without invasion [73].…”

“…Tumor tissue Overexpression of MMP-7 predicts presence of lymph node metastasis Okayama et al [72] Tumor tissue MMP-7 levels are higher in gastric cancer with vascular invasion compared to the group without invasion Yamashita et al [73] Colorectal cancer Serum MMP-7 is an independent prognostic factor for survival in advanced colorectal cancer, possibly even more accurate than LDH Miao et al carried out a meta-analysis of 14 clinical cohort studies (number of tumor samples included in the study, i.e., 935, was meaningful), discussing MMP-7 expression in esophageal cancer. The results were promising-they showed an obvious correlation between overexpression of MMP-7 and higher TNM (T-tumor, N-nodus, M-metastases) stages, higher invasive grade, and presence of lymph nodes metastasis [71].…”

Association of CDX2 and mucin expression with chemotherapeutic benefits in patients with stage II/III gastric cancer

“…We showed that gastric adenocarcinoma without CDX2 expression was associated with an increased likelihood of poor differentiation, which is in concordance with several previous studies 5,9 . Inconsistent with our findings, several studies showed that CDX2 expression was significantly associated with sex, 21 vascular invasion, 22 and tumor stage 23,24 . Meanwhile, some studies also support our findings of no association of CDX2 expression with sex, 24 clinical stage, 25,26 or vascular invasion 16,21,27 .…”

Contribution of Matrix Metalloproteinase-7 Genotypes to Endometriosis Risk in Taiwan

“…These extracellular matrix components are produced by various cancer cells, including breast, gastrointestinal, prostate, and endometrial tumor cells (58). MMP7 has been reported to be expressed by several types of cancer cells, such as lung (59), breast (60), head and neck (61), gastric (62), liver (63), pancreatic (64), colorectal (65) and most noticeable endometrial cancer (65). Thus, MMP7 is considered a practical marker and a potential therapeutic target for intervention.…”