Insulin-like growth factor binding protein-3 gene methylation and protein expression in gastric adenocarcinoma

Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Lisboa, Luara Carolina Frias; Silva, Patricia Natalia Oliveira; Chen, Elizabeth; Lima, Eleonidas Moura; Calcagno, Danielle Queiroz; Assumpção, Paulo Pimentel de; Burbano, Rommel Rodrı́guez; Smith, Marı́lia de Arruda Cardoso

doi:10.1016/j.ghir.2010.02.005

Cited by 18 publications

(10 citation statements)

References 39 publications

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“…In a previous study by our group in gastric tissue, we have not observed any differences of methylation with age [19]. This finding may be due to tissue-specific epigenetic regulation [20].…”

Section: Discussioncontrasting

confidence: 44%

SIRT1, IGFBP-3 and CAV1 Promoter DNA Methylation in Aging

Gigek

Lisboa²,

Silva³

et al. 2014

Transl Med (sunnyvale)

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The human genome is a fragile and highly conserved structure that accumulates a wide range of damaging alterations with age. Long-term alterations in the transcriptional potential of a cell are heritable and these changes are called epigenetics. The most studied alteration is the DNA methylation, which can regulate gene expression, often blocking gene transcription. The relationship between epigenetics and aging was proposed many years ago, and a decrease in the genomic global DNA methylation with age was largely observed. In this study we describe the methylation status of SIRT1, IGFBP-3 and CAV1 in a young and an older group of healthy individuals by methylation-specific PCR. SIRT1and IGFBP-3 promoter methylation frequency was significantly higher in the older than in the young adult group. Moreover, when combining promoter methylation status of several genes we observed that the total number of methylated promoters more than 85% of older individuals presented 4 promoters against only 46% of young adults. These findings may suggest that with increasing age there is an epigenetic switching to gene repression. The understanding of age-related genes methylation status can lead to a better comprehension of the role of epigenetic variation in the aging process.

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Section: Discussioncontrasting

confidence: 44%

SIRT1, IGFBP-3 and CAV1 Promoter DNA Methylation in Aging

Gigek

Lisboa²,

Silva³

et al. 2014

Transl Med (sunnyvale)

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“…Functional IGFBP3 SNPs (rs2854744 and rs2960436) determining high IGFBP3 circulating levels were associated with favorable prognosis of patients with advanced gastric cancer receiving palliative chemotherapy [41]. However, another study showed the quite contrary results, suggesting that the expression of IGFBP3 was higher in tumor samples than that in normal mucosa (54 tumor samples and 20 adjacent normal samples, not matched), and positive expression of IGFBP3 was associated with advanced histological grade, lymph node metastasis and distant metastasis without significant difference [42]. The possibility of intratumor heterogeneity and enrolled criteria may induce different results in different clinical studies.…”

Section: Discussionmentioning

confidence: 99%

IGFBP3, a Transcriptional Target of Homeobox D10, Is Correlated with the Prognosis of Gastric Cancer

et al. 2013

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Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element “TTAT”. Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p<0.001). Moreover, IGFBP3 expression was significantly lower in gastric tumor with lymph node metastasis compared with that without lymph node metastasis (p=0.045). Patients with high expression level of IGFBP3 showed favorable 5 year overall survival (p=0.011). Knockdown of IGFBP3 accelerated gastric cancer cell migration and invasion and induced the expression of invasive factors including MMP14, uPA and uPAR. Thus, our data suggest that HoxD10-targeted gene IGFBP3 may suppress gastric cancer cell invasion and favors the survival of gastric cancer patients.

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“…CCL20/MIP-3α has been known to be expressed in inflamed gastric tissue and plays a role in H.pylori induced gastritis [39]. Using IHC, IGFBP3 was found to be overexpressed in gastric cancers relative to the normal gastric tissue [40]. SPP1/OPN has also been reported to be overexpressed in gastric cancers and increasing levels have been detected with progression of disease [41].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of genes involved in gastric tumorigenesis

Rajkumar

Vijayalakshmi²,

Gopisetty³

et al. 2010

Cancer Cell Int

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BackgroundGastric cancer is one of the common cancers seen in south India. Unfortunately more than 90% are advanced by the time they report to a tertiary centre in the country. There is an urgent need to characterize these cancers and try to identify potential biomarkers and novel therapeutic targets.Materials and methodsWe used 24 gastric cancers, 20 Paired normal (PN) and 5 apparently normal gastric tissues obtained from patients with non-gastric cancers (Apparently normal - AN) for the microarray study followed by validation of the significant genes (n = 63) by relative quantitation using Taqman Low Density Array Real Time PCR. We then used a custom made Quantibody protein array to validate the expression of 15 proteins in gastric tissues (4 AN, 9 PN and 9 gastric cancers). The same array format was used to study the plasma levels of these proteins in 58 patients with gastric cancers and 18 from patients with normal/non-malignant gastric conditions.ResultsSeventeen genes (ASPN, CCL15/MIP-1δ, MMP3, SPON2, PRSS2, CCL3, TMEPAI/PMEPAI, SIX3, MFNG, SOSTDC1, SGNE1, SST, IGHA1, AKR1B10, FCGBP, ATP4B, NCAPH2) were shown to be differentially expressed between the tumours and the paired normal, for the first time. EpCAM (p = 0.0001), IL8 (p = 0.0003), CCL4/MIP-1β (p = 0.0026), CCL20/MIP-3α (p = 0.039) and TIMP1 (p = 0.0017) tissue protein levels were significantly different (Mann Whitney U test) between tumours versus AN & PN. In addition, median plasma levels of IL8, CXCL9/MIG, CCL3/MIP-1α, CCL20/MIP-3α, PDGFR-B and TIMP1 proteins were significantly different between the non-malignant group and the gastric cancer group. The post-surgical levels of EpCAM, IGFBP3, IL8, CXCL10/IP10, CXCL9/MIG, CCL3/MIP-1α, CCL20/MIP-3α, SPP1/OPN and PDGFR-B showed a uniform drop in all the samples studied.ConclusionsOur study has identified several genes differentially expressed in gastric cancers, some for the first time. Some of these have been confirmed at the protein level, as well. Some of these proteins will need to be evaluated further for their potential as diagnostic biomarkers in gastric cancers and some could be useful as follow-up markers in gastric cancer.

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Insulin-like growth factor binding protein-3 gene methylation and protein expression in gastric adenocarcinoma

Cited by 18 publications

References 39 publications

SIRT1, IGFBP-3 and CAV1 Promoter DNA Methylation in Aging

SIRT1, IGFBP-3 and CAV1 Promoter DNA Methylation in Aging

IGFBP3, a Transcriptional Target of Homeobox D10, Is Correlated with the Prognosis of Gastric Cancer

Identification and validation of genes involved in gastric tumorigenesis

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