Matrix metalloproteinase‐12 is associated with overall survival in Chinese patients with gastric cancer

Zheng, Jun; Chu, Dake; Wang, Desheng; Zhu, Yong; Zhang, Xiaoyin; Ji, Gang; Zhao, Haihong; Wu, Guoying; Du, Jianjun; Zhao, Qingchuan

doi:10.1002/jso.23302

Cited by 20 publications

(22 citation statements)

References 29 publications

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“…So it would contribute to identify high-risk patients who should receive more aggressive therapy, thus improve the prognosis of patients who received curative surgery. This prognostic value of MMP-12 in melanoma detected by the present study was consistent with findings in hepatocellular carcinoma, endometrial adenocarcinoma, and gastric cancer [13,16,17]. The possible explanation for the significant association of MMP-12 with melanoma progression and prognosis could attribute to the degradation of ECM and basement membrane by active MMP-12, which facilitate tumor cell invasion and metastasis.…”

Section: Discussionsupporting

confidence: 91%

“…Active MMP-12 has broad substrate specificity, recognizing extracellular matrix proteins such as type I gelactin, fibronectin, laminin, vitronectin, proteoglycans, and fibrin, and it can also produce angiostatin from plasminogen. Expression of MMP-12 in vivo has previously been described in hepatocellular carcinoma, colorectal cancer, gastric cancer, renal cell carcinomas, pancreatic cancer, and in esophageal carcinoma [13][14][15][16][17][18]. However, the role of MMP-12 on cancer, favorable or unfavorable for tumor invasion and metastasis, seems to be tissue-type specific.…”

Section: Introductionmentioning

confidence: 98%

“…In hepatocellular carcinoma and colorectal cancer, increased MMP-12 expression was found to be associated with better prognosis [19,20]. In contrast, in non-small cell lung cancer and gastric cancer, MMP-12 was highly expressed and strongly correlates with tumor recurrence as well as metastatic disease [16,21]. In human skin squamous cell carcinoma, MMP-12 expression could be detected in vivo and in vitro, and the expression level of MMP-12 was found to be related to histologic aggressiveness of tumor [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Matrix metalloproteinase-12 expression is increased in cutaneous melanoma and associated with tumor aggressiveness

et al. 2015

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Cutaneous melanoma is the most malignant form of skin cancer characterized by aggressive invasion. Matrix metalloproteinases play essential roles in tumor invasion due to their ECM degrading capacity. However, the clinical significance of matrix metalloproteinasis (MMP)-12 in human cutaneous melanoma has not been addressed yet. In the present study, we investigated MMP-12 expression level in 298 patients with cutaneous melanoma and 60 normal skin tissue specimens by immunohistochemistry assay. Appropriate statistical analysis was utilized to determine the association of MMP-12 with clinical features and prognosis of melanoma. Results showed that MMP-12 expression was increased in cutaneous melanoma compared with that in normal skin. It was also found that MMP-12 expression in melanoma was significantly associated with tumor invasion and metastasis. Univariate survival analysis indicated that patients with melanoma of high MMP-12 expression had unfavorable overall survival compared with those of low MMP-12 expression. Cox's proportional hazards analysis showed that MMP-12 expression was an independent prognostic marker of overall survival for patients with cutaneous melanoma. These results proved that MMP-12 expression was increased in cutaneous melanoma and associated with tumor progression. It also provided the first evidence that MMP-12 level could be an independent prognostic marker for patients with cutaneous melanoma.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Matrix metalloproteinase-12 expression is increased in cutaneous melanoma and associated with tumor aggressiveness

et al. 2015

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“…[30,31] Interestingly, 25.5% of these genes were primarily involved in cell adhesion, cell migration, extracellular matrix disassembly, blood vessel development, and wound healing associated with gastric adenocarcinoma metastases, such as collagen families, [20,23,32,33] fibronectin 1, [20,23,34] and matrix metalloproteinases (MMPs) families. [20,23,35–39] Some cell proliferation-related genes, such as MYC, [20,23,40] cyclin E1, [20,23,41] CDC28 protein kinase regulatory subunit 1, [20,42,43] CDC28 protein kinase regulatory subunit 2, [23,43] cyclin-dependent kinase 4, [20,23,44] and proliferating cell nuclear antigen, [20,44,45] EGFR, [20,44,46] FGFR4, [20,23] insulin like growth factor 2, [20] cell division cycle 25B, [47] human epidermal growth factor receptor 2, [44,45] and protein kinase, DNA-activated, catalytic polypeptide, [48] have been previously reported as showing extremely high levels of expression in gastric adenocarcinoma. A total of 37 genes, established in a large number of experimental and clinical studies, were selected for further study.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

et al. 2016

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“…In gastric cancer patients, prognostic markers, including erb-b2 receptor tyrosine kinase 2 (ERBB2) (26,27), CD44 (28,29) and matrix metallopeptidase 12 (30) have been reported. Additionally, a previous study by the present team demonstrated that the expression of the microRNAs mir-20b and mir-150 may be a prognostic marker for undifferentiated gastric cancer (1).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer

et al. 2016

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Abstract. Recent studies have shown constitutive activation of the Notch signaling pathway in various types of malignancies. However, it remains unclear whether this signaling pathway is activated in gastric cancer. In the present study, the aim was to investigate the role of Notch signaling in gastric cancer by investigating the subcellular localization of Notch-associated proteins in tissue samples from gastric cancer patients. Samples were obtained from 115 gastric cancer patients who had undergone surgery at the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science without pre-operative chemotherapy or radiation. Subsequently the correlation between translocation of NOTCH1 intracellular cytoplasmic domain (NICD) into the nucleus (as measured by immunostaining) and survival in gastric cancer patients after surgery was investigated. The results were analyzed in reference to the patients' clinicopathological characteristics and the effects of these results on patient prognosis were determined. Significant correlations were observed between NICD nuclear localization and clinicopathological characteristics, such as tumor status (T factor), lymph node status (N factor), pathological stage and differentiation status. No significant correlations were observed between NICD nuclear localization and age, gender, tumor location, vein invasion or lymphatic invasion. Patients with >30% of cancer cell nuclei positively stained for NICD (as revealed by immunostaining) were associated with a significantly shorter survival following surgery than patients with <30% NICD-positive cancer cell nuclei (log-rank test, P=0.0194). Univariate analysis revealed that among the clinicopathological factors examined, T factor [risk rate (RR)=10.870; P=0.0016], N factor (RR=41.667; P=0.0003), lymphatic invasion (RR=13.158; P=0.0125), vein invasion (RR=25.000; P= 0.0019) and translocation of NICD to the nucleus (RR=3.937; P=0.0312) were all identified to be statistically significant prognostic factors. However, multivariate analysis revealed that translocation of NICD to the nucleus was not independently associated with an unfavourable prognosis in patients with gastric cancer. The present results suggest that NOTCH1 acts as an oncogene in gastric cancer. It is hypothesized that translocation of NICD into the nucleus may be used as a therapeutic target in gastric cancer.

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Matrix metalloproteinase‐12 is associated with overall survival in Chinese patients with gastric cancer

Abstract: The study results showed that increased expression of MMP-12 was associated with tumor progression in gastric cancer. It also provided the first evidence for MMP-12 expression in gastric cancer as an independent prognostic factor.

Cited by 20 publications

References 29 publications

Matrix metalloproteinase-12 expression is increased in cutaneous melanoma and associated with tumor aggressiveness

Matrix metalloproteinase-12 expression is increased in cutaneous melanoma and associated with tumor aggressiveness

Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer

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