S100A6 Overexpression Is Associated with Poor Prognosis and Is Epigenetically Up-Regulated in Gastric Cancer

Wang, Xiaohong; Zhang, Lianhai; Zhong, Xi‐Yao; Xing, Xiaofang; Liu, Yiqiang; Niu, Zhaojian; Peng, Yong; Du, Hong; Zhang, Guiguo; Ying, Hanjie; Ni, Lei; Zhu, Yubing; Ge, Shaohua; Zhao, Wei; Lü, Aiping; Li, Jiyou; Ji, Jiafu

doi:10.2353/ajpath.2010.091217

Cited by 70 publications

(53 citation statements)

References 49 publications

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“…Heterogeneity of DNA methylation was also observed in our previous report [17]. In several cancers, the methylation status of specific genes correlates with disease progression [39][40][41][42]. The variable methylation profile of the genes we studied may reflect an intermediate state of progression and prognosis of leiomyoma.…”

Section: Discussionmentioning

confidence: 71%

Disease-dependent Differently Methylated Regions (D-DMRs) of DNA are Enriched on the X Chromosome in Uterine Leiomyoma

Maekawa

Yagi

Ohgane

et al. 2011

Journal of Reproduction and Development

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Abstract. Uterine leiomyoma is the most common benign tumor in women. Although responsible gene mutations have not been found in leiomyomas, they represent a progressive disease with irreversible symptoms. To characterize epigenetic features of uterine leiomyomas, the DNA methylation status of a paired sample of leiomyoma and normal myometrium was subjected to a microarray-based DNA methylation analysis with restriction tag-mediated amplification (D-REAM). In the leiomyoma, we identified an aberrant DNA methylation status for 463 hypomethylated and 318 hypermethylated genes. Although these changes occurred on all chromosomes, aberrantly hypomethylated genes were preferentially located on the X chromosome. Using paired samples of normal myometrium and leiomyoma from 6 hysterectomy patients, methylation-sensitive quantitative real-time PCR revealed 14 shared X chromosome genes with an abnormal DNA hypomethylation status (FAM9A, CPXCR1, CXORF45, TAF1, NXF5, VBP1, GABRE, DDX53, FHL1, BRCC3, DMD, GJB1, AP1S2 and PCDH11X) and one hypermethylated locus (HDAC8). Expression of XIST, which is involved in X chromosome inactivation, was equivalent in the normal myometrium and leiomyoma, indicating that the epigenetic abnormality on the X chromosome did not result from aberration of XIST gene expression. Based on these data, a unique epigenetic signature for uterine leiomyomas has emerged. The 14 hypomethylated and one hypermethylated loci provide valuable biomarkers for understanding the molecular pathogenesis of leiomyoma. Key words: Disease-dependent differently methylated regions (D-DMRs), DNA methylation, Epigenetics, Leiomyoma, X chromosome (J. Reprod. Dev. 57: 604-612, 2011) terine leiomyomas are the most common uterine tumors in reproductive-age women with a prevalence of 20-25% [1]. Leiomyomas frequently cause serious gynecological problems such as pelvic pain, menorrhagia, dysmenorrhea, infertility and recurrent pregnancy loss [2,3]. In addition, uterine leiomyomas are the most common indication for hysterectomy.Despite their high prevalence rate and distressing effect on women's reproduction, the pathogenesis of uterine leiomyomas remains unclear. Factors such as African descent, high body mass index, meat consumption, early menarche, hypertension and a history of pelvic inflammatory disease place women at greater risk for uterine leiomyoma. In contrast, women using hormonal contraception, who smoke, are parous and who consume green vegetables have lower risk [4][5][6]. These findings suggest that uterine leiomyomas develop not only by inherited genomic abnormalities but also by unfavorable environmental exposures.DNA methylation is one of the most well-characterized epigenetic marks. It is involved in gene-silencing, gene-stability and DNA duplication [7][8][9]. DNA methylation profiles define and distinguish between each type of normal cell [10,11] and have been used to characterize abnormal cells [8]. For each cell type, establishing and maintaining the specific DNA methylation profile of the cells is nece...

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Section: Discussionmentioning

confidence: 71%

Disease-dependent Differently Methylated Regions (D-DMRs) of DNA are Enriched on the X Chromosome in Uterine Leiomyoma

Maekawa

Yagi

Ohgane

et al. 2011

Journal of Reproduction and Development

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“…The function is not clear, but studies have suggested that it may be involved in cell proliferation and carcinogenesis, and as a diagnostic marker, especially in prognosis (Vimalachandran et al 2005;Wang et al 2010). Therefore, this gene would be a promising candidate biomarker of OV-associated CCA.…”

Section: Discussionmentioning

confidence: 94%

Candidate genes involving in tumorigenesis of cholangiocarcinoma induced by Opisthorchis viverrini infection

Boonmars

Boonjaraspinyo

et al. 2011

Parasitol Res

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Opisthorchiasis-associated cholangiocarcinoma (CCA) is one of main public health problems in Opisthorchis viverrini endemic areas. Although the definite relationship between prevalence of CCA and the parasite infection has been demonstrated, the molecular mechanism of tumorigenesis is still unknown. In the present study, by using animal model of opisthorchiasis-associated CCA, a kinetic analysis of cDNA microarray was performed to screen the candidate genes that involve in the development of opisthorchiasis-associated CCA. Microarray analysis revealed that the expressions of 131 genes were up-regulated during the development of CCA, including the genes relative to cell proliferation, differentiation and transformation, cell growth and cycle regulation, apoptosis, DNA repair, and cytoskeletal structure. The expressions of 145 genes were down-regulated, including the genes relative to metabolic enzymes, tumor suppressor, apoptosis, and oxidative response and oxidation reduction. The present study listed up the candidate genes involving tumorigenesis, provided molecular information on the development of opisthorchiasis-associated CCA and the potential biomarkers for diagnosis and therapy, and suggested that the increased expression of cell differentiation, proliferation, transformation-related genes, and decreased expression of metabolic enzymes may play important roles in the tumorigenesis of CCA.

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“…52 Unfortunately, little is still known about the exact mechanism of S100-A6 with regard to an aggressive tumor phenotype. Nevertheless, our observations support the general findings that S100-A6 plays an important role in the progression and prognosis in gastric cancer patients.…”

Section: Discussionmentioning

confidence: 99%

MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer

Balluff

Rauser

Meding

et al. 2011

The American Journal of Pathology

126

109

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Proteomics-based approaches allow us to investigate the biology of cancer beyond genomic initiatives. We used histology-based matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to identify proteins that predict disease outcome in gastric cancer after surgical resection. A total of 181 intestinal-type primary resected gastric cancer tissues from two independent patient cohorts were analyzed. Protein profiles of the discovery cohort (n ‫؍‬ 63) were directly obtained from tumor tissue sections by MALDI imaging. A seven-protein signature was associated with an unfavorable overall survival independent of major clinical covariates. The prognostic significance of three individual proteins identified (CRIP1, HNP-1, and S100-A6) was validated immunohistochemically on tissue microarrays of an independent validation cohort (n ‫؍‬ 118). Whereas HNP-1 and S100-A6 were found to further subdivide early-stage (Union Internationale Contre le Cancer [UICC]-I) and late-stage (UICC II and III) cancer patients into different prognostic groups, CRIP1, a protein previously unknown in gastric cancer, was confirmed as a novel and independent prognostic factor for all patients in the validation cohort. The protein pattern described here serves as a new independent indicator of patient survival complementing the previously known clinical parameters in terms of prognostic relevance. These results show that this tissue-based proteomic approach may provide clinically relevant information that might be beneficial in improving risk stratification for gastric cancer patients.

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S100A6 Overexpression Is Associated with Poor Prognosis and Is Epigenetically Up-Regulated in Gastric Cancer

Cited by 70 publications

References 49 publications

Disease-dependent Differently Methylated Regions (D-DMRs) of DNA are Enriched on the X Chromosome in Uterine Leiomyoma

Disease-dependent Differently Methylated Regions (D-DMRs) of DNA are Enriched on the X Chromosome in Uterine Leiomyoma

Candidate genes involving in tumorigenesis of cholangiocarcinoma induced by Opisthorchis viverrini infection

MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer

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