Role of<i>BMP3</i>in progression of gastric carcinoma in Chinese people

Chen, Xuerong; Wang, Jinwei; Li, Xiang; Zhang, Hong; Ye, Zai-yuan

doi:10.3748/wjg.v16.i11.1409

Cited by 17 publications

(16 citation statements)

References 21 publications

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“…In vitro studies have also suggested a role for BMP3 as a negative growth regulator in bone marrow progenitor cells through the inhibition of DNA synthesis and proliferation (16). Additionally, recent studies have revealed that BMP3 contributes to tumor development and progression (17)(18)(19). However, to the best of our knowledge, no study of a possible genetic association between polymorphisms in BMP3 and cancer has been conducted.…”

Section: Introductionmentioning

confidence: 87%

“…Although the role of BMP3 in the pathogenesis of cancer is unknown, several studies have demonstrated that BMP3 participates in the development of various types of cancer (17)(18)(19)(20)(21). Loh et al (17) reported that in colon cancer cell lines with methylation-dependent BMP3 downregulation, cell colony growth suppression was observed following the reintroduction of BMP3 coding sequences.…”

Section: Discussionmentioning

confidence: 99%

“…Loh et al (17) reported that in colon cancer cell lines with methylation-dependent BMP3 downregulation, cell colony growth suppression was observed following the reintroduction of BMP3 coding sequences. Methylation of the BMP3 promoter has also been described in subtypes of stomach (18), lung (20), pancreatic (19) and breast cancers (21) with downregulated BMP3 expression. Considering the results of these previous studies, we speculated that BMP3 is also involved in the development of PTC.…”

Section: Discussionmentioning

confidence: 99%

“…Extrathyroidal invasion is one of the most prominent prognostic risk factors for a poor clinical outcome in patients with PTC (22). As mentioned, BMP3 may negatively regulate cellular processes including migration, proliferation and differentiation (16)(17)(18)(19). In addition, BMP3 gene expression has been identified to be downregulated with hypermethylation of the BMP3 promoter region in various types of cancer (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned, BMP3 may negatively regulate cellular processes including migration, proliferation and differentiation (16)(17)(18)(19). In addition, BMP3 gene expression has been identified to be downregulated with hypermethylation of the BMP3 promoter region in various types of cancer (17)(18)(19). The SNP rs13138132 is located in a predicted promoter enhancing region (http://asia.ensembl.org/index.html); thus, we speculated that rs13138132 affects promoter activity and methylation of the BMP3 gene, and that rs13138132 eventually contributes to extrathyroidal invasion in PTC.…”

Section: Discussionmentioning

confidence: 99%

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Polymorphisms in bone morphogenetic protein 3 and the risk of papillary thyroid cancer

Kim¹,

Hong

Eun

et al. 2012

Oncology Letters

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Abstract. Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta (TGFβ) superfamily with well-described functions in bone formation. Although disrupted BMP signaling in tumor development has been investigated, a genetic association for BMP3 in papillary thyroid cancer (PTC) has remained largely unexplored. In this study, we investigated whether BMP3 single nucleotide polymorphisms (SNPs) are associated with the development of PTC and its clinicopathological features. A total of 103 PTC patients and 324 control subjects were enrolled. One promoter SNP (rs13138132; -1919C/A) and one missense mutation (rs3733549; Arg192Gln) in BMP3 were genotyped by direct sequencing. SNPStats, SNPAnalyzer, Helixtree and Haploview version 4.2 were used to evaluate the genetic data. Multiple logistic regression models were used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and P-values. The missense SNP (rs3733549) was weakly associated with the development of PTC in a codominant model (AA vs. GG; P=0.017) and a recessive model (AA vs. GG/GA; P=0.023). Additionally, in an analysis according to clinicopathological features, rs13138132 was significantly associated with extrathyroidal invasion in a codominant model (CA vs. CC; P=0.006) and a dominant model (CA/AA vs. CC; P=0.0023). We also identified that the frequency of the A allele in the promoter SNP (rs13138132) was increased in PTC patients with extrathyroidal invasion (P=0.004). Our data suggest that rs3733549 in BMP3 is associated with the development of PTC and that the A allele of rs13138932 in BMP3 is a risk factor for extrathyroidal invasion. IntroductionThyroid cancer is the most common type of endocrine malignancy, accounting for approximately 1% of all cases of cancer. It is the most rapidly increasing cancer among females and the second most rapidly increasing cancer among males. Histologically, thyroid cancer is classified as papillary thyroid cancer (PTC), follicular thyroid cancer, medullary thyroid cancer or undifferentiated or anaplastic thyroid cancer. Of these, PTC is the most common type, and it accounts for 85-90% of all thyroid malignancies (1,2). Although the etiology of PTC is unclear, environmental factors, including radiation, diet, smoking and hormones, have been identified to affect the pathogenesis of thyroid cancer (3,4). Genetic predisposition has also been implicated as a risk factor for thyroid cancer development (5,6).Bone morphogenic proteins (BMPs) have been demonstrated to play an important role during development (particularly during bone formation) and in the regulation of various cellular processes, including cell proliferation, apoptosis and differentiation (7). Evidence suggests that BMPs are important in tumorigenesis (8-10). BMPs are members of the transforming growth factor beta (TGFβ) family; thus, BMPs utilize a similar signaling cascade to that of TGFβ. BMPs have been identified to utilize the SMAD signaling pathway for their growth suppressive effects, and also to affect PTEN and p21 (W...

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Section: Introductionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Polymorphisms in bone morphogenetic protein 3 and the risk of papillary thyroid cancer

Kim¹,

Hong

Eun

et al. 2012

Oncology Letters

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Stool DNA testing for the detection of pancreatic cancer

Kisiel

Yab

Taylor

et al. 2011

Cancer

107

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BACKGROUND Pancreatic cancer (PanC) presents at late stage with high mortality. Effective early detection methods are needed. Aberrantly methylated genes are unexplored as markers for noninvasive detection by stool testing. We aimed to select discriminant methylated genes and to assess accuracy of these and mutant KRAS in stool to detect PanC. METHODS Nine target genes were assayed by real-time methylation-specific PCR (MSP) in bisulfite-treated DNA from microdissected frozen specimens of 24 PanC cases and 30 normal colon controls. Archived stools from 58 PanC cases and 65 controls matched on sex, age, and smoking were analyzed. Target genes from fecal supernatants were enriched by hybrid capture, bisulfite-treated, and assayed by MSP. KRAS mutations were assayed using the QuARTS technique. RESULTS Areas under the receiver operating characteristics curves (AUCs) for tissue BMP3, NDRG4, EYA4, UCHL1, MDFI, Vimentin, CNTNAP2, SFRP2 and TFPI2 were 0.90, 0.79, 0.78, 0.78, 0.77, 0.77, 0.69, 0.67, and 0.66, respectively. The top 4 markers and mutant KRAS were evaluated in stool. BMP3 was the most discriminant methylation marker in stool. At 90% specificity: methylated BMP3 alone detected 51% of PanCs, mutant KRAS detected 50%, and combination detected 67%. AUCs for methylated BMP3, mutant KRAS, and combination in stool were 0.73, 0.75, and 0.85, respectively. CONCLUSIONS This study demonstrates that stool assay of a methylated gene marker can detect PanC. Among candidate methylated markers discriminant in tissue, BMP3 alone performed well in stool. Combining methylated BMP3 and mutant KRAS increased stool detection over either marker alone.

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A systematic review and quantitative assessment of methylation biomarkers in fecal DNA and colorectal cancer and its precursor, colorectal adenoma

Liu

Long

et al. 2019

Mutation Research/Reviews in Mutation Research

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Role ofBMP3in progression of gastric carcinoma in Chinese people

Abstract: Promotor region methylation of the BMP3 gene may cause gastric carcinoma in Chinese people.

Cited by 17 publications

References 21 publications

Polymorphisms in bone morphogenetic protein 3 and the risk of papillary thyroid cancer

Polymorphisms in bone morphogenetic protein 3 and the risk of papillary thyroid cancer

Stool DNA testing for the detection of pancreatic cancer

A systematic review and quantitative assessment of methylation biomarkers in fecal DNA and colorectal cancer and its precursor, colorectal adenoma

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