Aberrant Methylation of Suppressor of Cytokine Signaling 1 (SOCS1) Gene as a Biomarker for Early Prediction and Diagnosis of Bladder Cancer

Guan, Hongjun; Li, Xiaoxia; Lü, Junhua; Meng, Lili; Guo, Yupeng; Dong, Jing; Rong, Shengzhong; Zhao, Fuyang; Shen, Hongmei

doi:10.7754/clin.lab.2019.190926

Cited by 3 publications

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“…Six principal component factors were extracted by combining initial eigenvalue, explanatory power, and Scree Plot. Factor tion and BCa was also found in our previous research [22]. However, its methylation pattern is still unclear.…”

Section: Resultssupporting

confidence: 76%

“…We also followed up 143 bladder cancer patients after surgery. According to the cut-off value [22], the subjects were divided into two groups. There were 51 cases in the hypomethylation group (CpG island methylation rate <10.93%) and 92 cases (CpG island methylation rate ≥10.93%) in the hypermethylated group.…”

Section: Resultsmentioning

confidence: 99%

“…The DNA concentration and purity were measured by the NanoDrop one. According to the primer sequence, PCR reaction system and method determined in our previous study [22], we carried out experiments to detect the methylation level of CpG island in the promoter region of the SOCS1 gene. All PCR amplifications were repeated.…”

Section: Methodsmentioning

confidence: 99%

“…The transcriptional activity of SOCS1 is regulated by transcriptional silencing due to the methylation status [21]. We had previously reported that the methylation of SOCS1 was associated with BCa [22]. But its function and possible role in BCa pathogenesis are still unknown.…”

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confidence: 99%

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DNA methylation patterns of SOCS1 gene in peripheral blood identifies risk loci associated with bladder cancer based on principal component analysis

Guan¹,

Lü²,

Qu³

et al. 2021

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Bladder cancer (BCa) is a common carcinoma of the urinary tract, which occurs in the bladder mucosa. In recent years, people have recognized that epigenetic changes such as DNA methylation play important roles in the development of BCa but the specific mechanism is unclear. In this study, we detected the methylation rates in the SOCS1 gene of 490 subjects (including 247 patients with BCa and 243 healthy controls) using the MassARRAY EpiTYPER system. Principal component analysis (PCA) was conducted with the aim of identifying common underlying patterns that could explain the largest part of common variance in methylation across units. A logistic regression model was used to assess the relation of SOCS1 methylation patterns with factors related to BCa risk. The methylation rates varied for different CpG units and were significantly different in BCa patients compared to controls. Six principal component factors were extracted by combining initial eigenvalue, explanatory power, and Scree Plot. After adjusting for age, gender, family history of bladder cancer, smoking, and drinking, we observed that Factor 1 (OR=0.051, 95% CI: 0.015-0.178, p<0.001), Factor 2 (OR=0.146, 95% CI: 0.073-0.295, p<0.001), Factor 3 (OR=0.346, 95% CI: 0.198-0.606, p<0.001), and Factor 4 (OR=0.270, 95% CI: 0.135-0.537, p<0.001) were associated with BCa. Based on follow-up results, we found that the 1-, 3-, 5-year survival rates in the hypermethylated group were lower than in the hypomethylated group. We found that several CpG units in methylation patterns were associated with the incidence of BCa showing the important DNA methylation patterns for BCa pathogenesis. Our findings provided new insights into understanding this disease and new potential targets for therapeutic intervention for BCa patients in the future.

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Section: Resultssupporting

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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DNA methylation patterns of SOCS1 gene in peripheral blood identifies risk loci associated with bladder cancer based on principal component analysis

Guan¹,

Lü²,

Qu³

et al. 2021

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“…Indeed, although this drug is able to reduce the constitutive activation of STAT3, some cells still resist the treatment; thus, 5-AZA could help to potentiate the cytotoxic effects mediated by AG490. At the molecular level, 5-AZA increased the expression of SOCS3, known to be among the numerous targets of STAT3 and known to be able to negatively regulate its activation, suggesting that methylation of the SOCS3 promoter could contribute to STAT3 activation in PEL cells, as previously reported in bladder cancer cells in which hypermethylation of SOCS3 represents a prognostic biomarker [40]. Alongside STAT3, SOCS3 may interact with several other signaling pathways, affecting cancer diagnosis and prognosis [41].…”

Section: Discussionmentioning

confidence: 61%

5-AZA Upregulates SOCS3 and PTPN6/SHP1, Inhibiting STAT3 and Potentiating the Effects of AG490 against Primary Effusion Lymphoma Cells

Di Crosta,

Arena,

Benedetti

et al. 2024

CIMB

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Epigenetic modifications, including aberrant DNA methylation occurring at the promoters of oncogenes and oncosuppressor genes and histone modifications, can contribute to carcinogenesis. Aberrant methylation mediated by histone methylatransferases, alongside histones, can affect methylation of proteins involved in the regulation of pro-survival pathways such as JAK/STAT and contribute to their activation. In this study, we used DNA or histone demethylating agents, 5-Azacytidine (5-AZA) or DS-3201 (valemetostat), respectively, to treat primary effusion lymphoma (PEL) cells, alone or in combination with AG490, a Signal transducer and activator of transcription 3 (STAT3) inhibitor. Cell viability was investigated by trypan blue assay and FACS analysis. The molecular changes induced by 5-AZA and/or AG490 treatments were investigated by Western blot analysis, while cytokine release by PEL cells treated by these drugs was evaluated by Luminex. Statistical analyses were performed with Graphpad Prism® software (version 9) and analyzed by Student’s t test or a nonparametric one-way ANOVA test. The results obtained in this study suggest that 5-AZA upregulated molecules that inhibit STAT3 tyrosine phosphorylation, namely Suppressor of Cytokine Signaling 3 (SOCS3) and tyrosine–protein phosphatase non-receptor type (PTPN) 6/Src homology region 2 domain-containing phosphatase-1 (SHP-1), reducing STAT3 activation and downregulating several STAT3 pro-survival targets in PEL cells. As this lymphoma is highly dependent on the constitutive activation of STAT3, 5-AZA impaired PEL cell survival, and when used in combination with AG490 JAK2/STAT3 inhibitor, it potentiated its cytotoxic effect. Differently from 5-AZA, the inhibition of the EZH1/2 histone methyltransferase by DS-3201, reported to contribute to STAT3 activation in other cancers, slightly affected STAT3 phosphorylation or survival in PEL cells, either alone or in combination with AG490. This study suggests that 5-AZA, by upregulating the expression level of SOCS3 and PTPN6/SHP1, reduced STAT3 activation and improved the outcome of treatment targeting this transcription factor in PEL cells.

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Advancements in the clinical application of gene methylation for early cancer detection

Xu,

Guo,

Liu

et al. 2024

Front. Epigenet. Epigenom.

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This review provides an overview of common assays used to screen for gene methylation and early biomarkers of methylation in various cancers. DNA methylation, one of the most well-studied epigenetic modifications, plays a crucial role in normal cell and tissue development. It is increasingly utilized as a biomarker for early cancer and precancerous lesion detection. In this review, we describe common methods associated with gene methylation, including bisulfite sequencing PCR (BSP), pyrosequencing technology (PYR), methylation-specific polymerase chain reaction (MS-PCR/MSP), methylation-sensitive high-resolution melting (MS-HRM), methylation sensitive single nucleotide primer extension (MS-SnuPE), Epityper, Droplet digital PCR (ddPCR), methylation-sensitive restriction enzyme (MSRE) analysis, COBRA and PacBio SMRT sequencing. Additionally, we summarize methylation markers and their sample types for early cancer screening, focusing on colorectal cancer, hepatocellular carcinoma, gastric cancer, pancreatic cancer, esophageal cancer (digestive system), lung cancer (respiratory system), breast cancer, ovarian cancer, cervical cancer (female reproductive system), bladder cancer, and prostate cancer (urinary system). Furthermore, we discuss the recent detection of methylation biomarkers in clinical samples such as blood, urine, sputum, feces, and tissues. The aim of this review is to summarize early methylation biomarkers that are expected or have already been clinically applied. For future large-scale studies or the integration of available methylome level data, the discovery of sufficiently sensitive clinical biomarkers is essential.

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Aberrant Methylation of Suppressor of Cytokine Signaling 1 (SOCS1) Gene as a Biomarker for Early Prediction and Diagnosis of Bladder Cancer

Cited by 3 publications

References 0 publications

DNA methylation patterns of SOCS1 gene in peripheral blood identifies risk loci associated with bladder cancer based on principal component analysis

DNA methylation patterns of SOCS1 gene in peripheral blood identifies risk loci associated with bladder cancer based on principal component analysis

5-AZA Upregulates SOCS3 and PTPN6/SHP1, Inhibiting STAT3 and Potentiating the Effects of AG490 against Primary Effusion Lymphoma Cells

Advancements in the clinical application of gene methylation for early cancer detection

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