Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer

Yu, Fang; Zhang, Lu; Wang, G. Q.; Pan, Zhizhong; Zhou, Zhiwei; Yun, Jie; Zhang, M. F.; Wan, De Sen

doi:10.1007/s00384-009-0725-z

Cited by 168 publications

(150 citation statements)

References 57 publications

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“…In the current study we found that MMP-7 was overexpressed in 38.8% of CRCs and this positive rate is comparable with previous reports of 30% to 46% [15] [17] [30] [32]. In a recent study with a larger sample size of 620 cases, Fang et al reported MMP-7 immunopositivity in 88.8% of the cancer [33]. Roca and co-investigators demonstrated 81.7% of 60 CRC tumors were positive for MMP-7 [34].…”

Section: Discussionsupporting

confidence: 91%

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Naidu¹,

Nee²,

Jw³

et al. 2014

JCT

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Background: The purpose of the present study is to investigate the expression levels of STAT3, pSTAT3, MMP-7 and VEGF in colorectal adenocarcinoma, and also to determine association with the clinico-pathological parameters and co-expression of these genes. Methods: An immunohistochemical method was used to evaluate the expression of MMP-7 and VEGF genes in 93 archival tissues whereas STAT3 and pSTAT3 expression was determined in 75 cases. Results: Overexpression of STAT3 was detected in 26.7% (20/75), pSTAT3 in 13.4% (10/75), MMP-7 in 38.8% (36/93) and VEGF in 59.2% (55/93) of the colorectal carcinomas. STAT3, MMP-7 and VEGF immunopositivity were significantly correlated with poorly-differentiated tumors (P = 0.004; P = 0.03; P = 0.002, respectively) but not with other parameters. However, pSTAT3 immunostaining was not significantly associated with the clinico-pathological characteristics. Significant relationship was noted between overexpression of pSTAT3 and STAT3 (P < 0.001), pSTAT3 and VEGF (P = 0.044), pSTAT3 and MMP-7 (P = 0.003), and STAT3 and VEGF (P = 0.037) but marginal association was detected between STAT3 and MMP-7 (P = 0.057), and MMP-7 and VEGF (P = 0.052). Conclusion: Our data suggest that expression of these genes may have an important role in tumor dedifferentiation and may be useful as indicators of biologic aggressiveness. Co-expression of the bio-* Corresponding author. R. Naidu et al. 1176markers by cancer cells may have important implications in colorectal cancer biology and could be useful biological markers of the malignant phenotype.

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Section: Discussionsupporting

confidence: 91%

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Naidu¹,

Nee²,

Jw³

et al. 2014

JCT

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“…MMP7 was determined to be up-regulated in cirrhotic nodules (potential precursors of HCC), compared with normal liver, as well as in HCC (71). Furthermore, elevated MMP7 expression is correlated with decreased survival and increased recurrence and liver metastasis of colon cancer (72) and pancreatic carcinoma (73). Most importantly, MMP7 was demonstrated to promote in vitro invasiveness of cancer cells of the stomach, colon, and pancreas (reviewed in Ref.…”

Section: Table 3 Distribution Of Identified Mir-122 Targets Accordingmentioning

confidence: 99%

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122

Boutz

Collins

Suresh

et al. 2011

Journal of Biological Chemistry

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MicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporterbased screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function. MicroRNAs (miRNAs)4 are small (20 -24 nt) endogenously expressed noncoding RNAs that regulate the translational efficiency and/or degradation of specific mRNAs. First discovered in Caenorhabditis elegans (1), miRNAs have since been identified in a diverse set of eukaryotic organisms as well as viruses, with over 700 miRNAs currently identified in humans (2). miRNAs function via the RNAi pathway, guiding the RNAinduced silencing complex to mRNAs by Watson-Crick base pairing between the miRNA and target mRNA (reviewed in Ref.3). The resulting interaction leads to translational repression of the mRNA, although how this repression is achieved remains unclear. Several mechanisms have been proposed (reviewed in Ref. 4), and many questions remain; however, it is clear that sequence complementarity lies at the heart of miRNA function. In animals, sequence complementarity between an miRNA and its target mRNA is rarely perfect. The vast majority of binding sites contain mismatches between strands, and these mismatches have been shown to play an important functional role in target repression (5, 6). Imperfect complementarity allows for a greater variability of target sequences, thus increasing the number of potential binding sites for a given miRNA, with estimates of 300 -400 targets on average per miRNA (7). Although many potential miRNA targets can be identified through predictions, no computational approach is all-inclusive, and even highly conservative predictions must be validated by experimental means to verify functional relevance.Certain miRNAs have caught the attention of scientists due to their strong connections to diseases and cancer. Such is the

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“…Fang ve arkadaşlarının yaptığı bir başka çalışmada ise tumor dokusunda matrix metalloproteinaz-7 (MMP7) over ekspresyonunun karaciğer metastazını predikte etmede etkili olabileceği gösterilmiştir (OR 6,7, p=0,003) (17). Bu çalışmaların tamamında olası biyolojik markerların tamamı tümör dokusunda bakılmış olup kullanımları kısıtlı kalmıştır, bu sebeple tanı anında karaciğer metastazını predikte edebilecek kolay ulaşılabilir ve daha ucuz belirteçler gerekmektedir.…”

Section: Gereç Ve Yöntemunclassified

Predictive Factors Of Liver Metastasis After Curative Treatment For Colorectal Cancer

Hocazade¹,

Yıldırım²,

Bozkaya³

et al. 2016

Acta Oncol Tur.

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ÖZETGiriş ve Amaç: Kolorektal kanserler dünya genelinde en sık görülen kanserlerden biridir. Karaciğer metastazı tanıdan kısa bir süre sonra gelişebilir. Daha önce tedavi almış kolorektal kanserli hastalarda karaciğer metastazektomi yapılması 5 yıllık sağkalımı %20-40 oranında arttırabilir. Bu çalışmada erken evre kolorektal karsinomlu hastaların karaciğer nüksünü erken dönemde predikte edebilecek faktörleri araştırmayı amaçladık. Yöntem ve Gereçler: Çalışmamıza Ankara Numune Eğitim ve Araştırma Hastanesi Tıbbi Onkoloji Kliniğinde 2009 Ocak-2014 Ağustos aylarında takibe alınarak tedavi planı yapılan non-metastatik 517 hasta dahil edilmek üzere değerlendirildi. Birinci grupta karaciğer dışı nüksü olan hastalarla beraber nüks olmadan takibe devam edilen hastalar varken 2.grupta ise karaciğer metastazı gelişen hastalar mevcuttu. Hastaların tanı anındaki laboratuar sonuçları receiver operating characteristic (ROC) curve analizi uygulanarak laktat dehidrogenaz (LDH), karsinoembriyonik antijen (CEA) ve gama glutamil transferaz (GGT) için cut off değerleri belirlendi (sırasıyla, 400 U/L, 50 ng/ml ve 90 U/L). Bulgular: Univariate analizde CEA değeri yüksek olan 20 hastanın 7'sinde (%35), düşük olan 206 hastanın 28'inde (%8,7) kc metastazı gelişmişti (p<0,001). LDH değerine göre karaciğer nüksüne bakıldığında ise yüksek olan 15 hastanın 5'inde (%33,3), düşük olan hasta grubunda 189 hastadan 17'sinde (%9) takipte karaciğer metastazı gelişti (p=0,003). GGT değerine göre ise yüksek olan 15 hastanın 5'inde (%33,3), düşük olan 244 hastanın 24'ünde (%9,8) karaciğer nüksü gelişmişti (p=0,005). Multiple lojistik regresyon analizi ile değerlendirildiğinde LDH anlamlılığını korumaktaydı (p=0,047, OR 7,8: 1,02-59,3). Tartışma ve Sonuç: Karaciğer metastazı kolorektal kanser tanısı alan hastalarda surveyi etkileyen önemli bir faktördür. Bizim çalışmamızda LDH yükseliğinin karaciğer nüksünü predikte etmede kullanılabilecek uygun bir fakör olduğu görüldü fakat bu sonucun prospektif randomize çalışmalarla desteklenmesi gerekmektedir. Anahtar Kelimeler: Kolorektal kanser, karaciğer, nüks ABSTRACT Introductıon: Colorectal cancer (CRC) is one of the most commonly detected cancers worldwide. Liver metastasis might develop shortly after the diagnosis of colorectal cancer. Liver metastasectomy might improve the five year survival rate to 20-40% in patient with previously treated CRC. We aimed in this study to evaluate the predictive factors to liver metastases in patients with newly diagnosed non metastatic CRC. Methods: Five hundred and seventeen non-metastatic colorectal patients followed at Medical Oncology Department of Ankara Numune Training and Research Hospital between January 2009 and August 2014 were evaluated retrospectively. Patients were divided in to the two subgroups. Group 1 consisted of non-metastatic and metastatic patients except liver metastases. Group 2 consisted of patients with liver metastases. Laboratuary results at the time of diagnosis were evaluated with receiver operating characteristic (ROC) Curve analysis and cut...

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Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer

Abstract: We conclude that elevated survivin, MMP7, and TROP2 expression levels are related to decreased survival. In addition, elevated MMP7 and TROP2 expression levels are predictors of disease recurrence and liver metastasis, respectively.

Cited by 168 publications

References 57 publications

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122

Predictive Factors Of Liver Metastasis After Curative Treatment For Colorectal Cancer

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