Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients

Wang, Yucai; Yu, Zhenghong; Liu, Chang; Xu, Lizhi; Yu, Weiyang; Lu, Jia; Zhu, Ren-Min; Li, Guoli; Xia, Xinyi; Wei, Xiaowei; Ji, Hanxu; Lü, Hongyan; Gao, Yong; Gao, Weimin; Chen, Longbang

doi:10.3748/wjg.14.3074

Cited by 76 publications

(38 citation statements)

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“…It has been suggested that RASSF1A methylation is one of the most common aberrations so far identified in human cancers and that the loss of the functional protein may promote the development of many human tumors. Hypermethylation of the RASSF1A has been detected frequently in the tissues of different cancers [10][11][12][13][14][15][16][17], while in the body fluid, methylation of RASSF1A promoter has also been documented in 50% sputum and 84% serum from lung cancer [30], 35% urine from bladder cancer [15], 56-60% serum from breast caner [31][32][33], and 5% serum from undifferentiated nasopharyngeal carcinoma [34], which indicated the value of RASSF1A methylation in DNA for the early-stage diagnosis of tumors. Detection of methylated DNA has then been suggested as a potential biomarker for early detection of cancer.…”

Section: Discussionmentioning

confidence: 99%

“…There is no information presently available about the protein status of RASSF1A in liver tissue microarrays (TMAs). Recent studies have also shown that inactivation of RASSF1A promoter by methylation was detectable in tumor cell lines and tissues, such as lung [10], gallbladder [11], breast [12], kidney [13], prostate [14], endometrium [7], bladder [15], bile ducts [16], stomach [17], and colon and rectum carcinoma [17]. The hypermethylation of RASSF1A suggests new perspectives for the diagnosis of malignant tumor.…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathological significance of RASSF1A reduced expression and hypermethylation in hepatocellular carcinoma

Chen

et al. 2010

Hepatol Int

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Purpose Protein downregulation and hypermethylation of Ras association domain family 1A (RASSF1A) has been recognized as an important early event in different classes of carcinogenesis, but clinicopathological significance of RASSF1A protein expression and methylation in hepatocellular carcinoma (HCC) remains largely unknown. The aim of the study was to investigate the expression of RASSF1A protein and methylation in HCC and their clinical significance. Methods Immunohistochemistry was employed to detect the expression of RASSF1A proteins in liver tissue microarrays. Aberrant promoter hypermethylation of RASSF1A was investigated in DNA from HCC, matching noncancerous tissues and serum of 35 HCC patients by methylation-specific PCR. Results RASSF1A protein expression in HCC was significantly lower than that in noncancerous (p = 0.015) and paracancerous tissues (p = 0.017). In addition, reduced RASSF1A protein expression is related to TNM stage, metastasis, a-fetoprotein, portal vein embolus, capsular infiltration, and multiple tumor nodes. Furthermore, RASSF1A promoter methylation in HCC was significantly higher than that in noncancerous liver tissues (p \ 0.05). Meanwhile, RASSF1A promoter hypermethylation was detected in 14 in the serum DNA from HCC patients, whereas no hypermethylation was detected in the normal controls. Hypermethylation of RASSF1A in HCC serum and tissues was negatively correlated with the expression of RASSF1A protein expression (p \ 0.05). Conclusions The loss or abnormal protein downregulation and the promoter hypermethylation of RASSF1A could play important roles in the tumorigenesis development and metastases of HCC. The detection of the promoter hypermethylation of RASSF1A in serum DNA could be a valuable biomarker for early-stage diagnosis in populations at high risk of HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinicopathological significance of RASSF1A reduced expression and hypermethylation in hepatocellular carcinoma

Chen

et al. 2010

Hepatol Int

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“…Prognostic values of promoter hypermethylation in patients with gastric cancer documented that patients with higher stage of colorectal cancer possess a higher concentration of methylated APC, TIMP-3 and hMLH1 in the serum [28] . Wang et al [29] reported a frequent hypermethylation of RASSF1A gene promoter in gastric and colon cancer and predicted its utility as a diagnostic marker.…”

Section: Chromatin Remodeling and Epigenetic Modifications As Etiologmentioning

confidence: 99%

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

Verma

Kesh

Ganguly

et al. 2014

WJBC

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teinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/ anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows. AbstractThe process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-

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“…In the present study, we found a higher methylation frequency of DLC1 gene promoter in the serum DNA from CRC patients, whereas it was rare in the serum of benign disease. The sensitivity, as well as the specificity was satisfactory compared with several other frequently methylated loci identified in plasma/serum of CRC, for example p15, p16, APC, hMLH1, MGMT, RASSF1A, RUNX3, SFRP1 and 2 [24][25][26] . Additionally, consistent with Zhang, et al [21] , we did not find any correlation between DLC1 methylation and clinicopathological features in CRC, which suggested DLC1 methylation might be a relatively early event during tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

Zou

Tang

et al. 2011

Chin. J. Cancer Res.

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Objective: Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal cancer (CRC). The aim of this study is to evaluate the diagnostic role of DLC1 gene methylation in the serum DNA from CRC patients.Methods: This study enrolled 85 CRC patients and 45 patients with benign colorectal diseases. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of DLC1 gene in serum DNA. The combination of DLC1 methylation and conventional tumor markers was further analyzed.Results: Hypermethylation of DLC1 was detected in 42.4% (36/85) of CRC serums, while seldom in the benign controls (8.9%, 4/45) (P<0.001). The aberrant DLC1 methylation in serum DNA was not associated with patients' clinicopathological features and elevated CEA/CA19-9 levels. Furthermore, the combinational analysis of CEA, CA19-9 and DLC1 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination for CRC diagnosis. Conclusion:The serum DLC1 methylation may be a promising biomarker for the early detection of CRC, which will further increase the diagnostic efficiency in combination with CEA and CA19-9.

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Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients

Cited by 76 publications

References 38 publications

Clinicopathological significance of RASSF1A reduced expression and hypermethylation in hepatocellular carcinoma

Clinicopathological significance of RASSF1A reduced expression and hypermethylation in hepatocellular carcinoma

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

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