Hypermethylation of the SPARC promoter and its prognostic value for prostate cancer

Liu, Tieshi; Qiu, Xuefeng; Zhao, Xiaozhi; Yang, Rong; Lian, Huibo; Qu, Feng; Li, Xiaogong; Guo, Hongqian

doi:10.3892/or.2017.6121

Cited by 15 publications

(9 citation statements)

References 25 publications

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“…Therefore, we believe that SPARC might play a role as a tumor suppressor gene in GC. SPARC has also been found to be downregulated in some other types of cancer, including neuroblastoma[16], ovarian cancer[17], pancreatic cancer[8], colon cancer[9], bladder cancer[18], prostate cancer[19], and acute leukemia[20]. When analyzing these tumors genetically, it is common to find that the promoter region of the SPARC gene in these tumors was in a state of abnormal hypermethylation.…”

Section: Discussionmentioning

confidence: 99%

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

Shao

Zhou

Dai

2019

WJG

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BACKGROUNDAberrant methylation in DNA regulatory regions could downregulate tumor suppressor genes without changing the sequences. However, our knowledge of secreted protein acidic and rich in cysteine (SPARC) and its aberrant methylation in gastric cancer (GC) is still inadequate. In the present research, we performed fundamental research to clarify the precise function of methylation on SPARC and its significance in GC.AIMTo investigate promoter methylation and the effects of the SPARC gene in GC cells and tissues and to evaluate its clinical significance.METHODSPlasmids that overexpressed the SPARC gene were transfected into human GC BGC-823 cells; non-transfected cells were used as a control group (NC group). Quantitative real-time polymerase chain reaction and western blotting (WB) were then used to detect the expression of SPARC. Methylation-specific polymerase chain reaction was executed to analyze the gene promoter methylation status. Cell viability was measured by the cell counting kit-8 assay. The migration and invasion ability of cells were detected by scratch assays and transwell chamber assays, respectively. Cell cycle events and apoptosis were observed with a flow cytometer.RESULTSThe expression of SPARC mRNA in GC tissues and cells was significantly lower and showed differing degrees of hypermethylation, respectively, than that in normal adjacent tissues and control cells. Treatment with 5-Aza-2’-deoxycytidine (5-Aza-Cdr) was able to restore the expression of SPARC and reverse promoter hypermethylation. Overexpression of the SPARC gene significantly inhibited proliferation, migration, and invasion of GC cells, while also causing cell cycle arrest and apoptosis; the NC group exhibited the opposite effects.CONCLUSIONThis study demonstrated that SPARC could function as a tumor suppressor and might be silenced by promoter hypermethylation. Furthermore, in GC cells, SPARC inhibited migration, invasion, and proliferation, caused cell cycle arrest at the G0/G1 phase, and promoted apoptosis.

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Section: Discussionmentioning

confidence: 99%

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

Shao

Zhou

Dai

2019

WJG

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“…24 SPARC expression was decreased in PCa cell lines because of hypermethylation of the SPARC promoter, and SPARC hypermethylation was correlated with a poorer prognosis in PCa patients. 25 In colorectal cancer (CRC), high stromal SPARC indicated poor prognosis in CRC patients, and fibroblast-derived SPARC enhanced tumor cell invasion; 26 however, other studies revealed that low expression of SPARC in CRC tissue is associated with poor prognosis and aggressive clinicopathological features. 27,28 In studying the relationship between SPARC and gynecological tumors, we also found contradictory results.…”

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confidence: 99%

<p>Low Levels of SPARC are Associated with Tumor Progression and Poor Prognosis in Human Endometrial Carcinoma</p>

Wang

2020

OTT

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Background SPARC (secreted protein acidic and rich in cysteine), also known as osteonectin, BM-40, and 43 K protein, is a matricellular protein associated with various tumor progressions. The aim of this research was to investigate the prognostic value of SPARC in endometrial carcinoma (EC) and its function in cancer cell invasion and metastasis. Methods From both mRNA and protein levels, SPARC expression in normal endometrial tissue and EC tissue, normal endometrial cells and 4 EC cell lines (KLE, HEC-1A, HEC-1B, Ishikawa) were evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC), quantitative real-time PCR (qRT-PCR) and Western blotting. RNA interference mediated by lentivirus was performed to get the stable SPARC down-expressing cells. The functional analysis techniques in vitro and in vivo were used to detect the effects of SPARC knockdown on EC cell proliferation, apoptosis, invasion and metastasis. Results The expressions of SPARC in EC tissues and cells were much lower than those in normal endometrial cells and tissues; meanwhile, its low expression was closely related to the malignant clinicopathological characteristics of EC. SPARC knockdown could inhibit apoptosis, promote the process of EMT and improve the proliferation and invasion capacities of EC cells in vitro and in vivo. Conclusion The low expression of SPARC was detected in EC tissues and cells, which was positively correlated with the poor prognosis of EC patients. SPARC acted as a tumor suppressor gene that hindered EC progression, which proposed a new therapeutic strategy for EC treatment.

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“…Second, wet experiments (IHC, qRT-PCR, overexpression, or knockdown) should be performed to elucidate the expression and roles of the signature genes in PCa because most of them were not reported previously and some were even contradictory. Third, the coexpression relationship between lncRNAs and mRNAs should be explored by chromatin immunoprecipitation, RNA immunoprecipitation, and biotin-labeled RNA pull-down assays [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Coexpression Network Analysis Identifies a Novel Nine-RNA Signature to Improve Prognostic Prediction for Prostate Cancer Patients

Cai

Chen

et al. 2020

BioMed Research International

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Background. Prostate cancer (PCa) is the most common malignancy and the leading cause of cancer death in men. Recent studies suggest the molecular signature was more effective than the clinical indicators for the prognostic prediction, but all of the known studies focused on a single RNA type. The present study was to develop a new prognostic signature by integrating long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) and evaluate its prognostic performance. Methods. The RNA expression data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA) or Gene Expression Omnibus database (GSE17951, GSE7076, and GSE16560). The PCa-driven modules were identified by constructing a weighted gene coexpression network, the corresponding genes of which were overlapped with differentially expressed RNAs (DERs) screened by the MetaDE package. The optimal prognostic signature was screened using the least absolute shrinkage and selection operator analysis. The prognostic performance and functions of the combined prognostic signature was then assessed. Results. Twelve PCa-driven modules were identified using TCGA dataset and validated in the GSE17951 and GSE7076 datasets, and six of them were considered to be preserved. A total of 217 genes in these 6 modules were overlapped with 699 DERs, from which a nine-gene prognostic signature was identified (including 3 lncRNAs and 6 mRNAs), and the risk score of each patient was calculated. The overall survival was significantly shortened in patients having the risk score higher than the cut-off, which was demonstrated in TCGA (p=5.063E−03) dataset and validated in the GSE16560 (p=3.268E−02) dataset. The prediction accuracy of this risk score was higher than that of clinical indicators (the Gleason score and prostate-specific antigen) or the single RNA type, with the area under the receiver operator characteristic curve of 0.945. Besides, some new therapeutic targets and mechanisms (MAGI2-AS3-SPARC/GJA1/CYSLTR1, DLG5-AS1-DEFB1, and RHPN1-AS1-CDC45/ORC) were also revealed. Conclusion. The risk score system established in this study may provide a novel reliable method to identify PCa patients at a high risk of death.

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Hypermethylation of the SPARC promoter and its prognostic value for prostate cancer

Cited by 15 publications

References 25 publications

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

<p>Low Levels of SPARC are Associated with Tumor Progression and Poor Prognosis in Human Endometrial Carcinoma</p>

Coexpression Network Analysis Identifies a Novel Nine-RNA Signature to Improve Prognostic Prediction for Prostate Cancer Patients

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