Hypomethylation of BORIS is a promising prognostic biomarker in hepatocellular carcinoma

He, Jingjing; Huang, Yuan; Liu, Zhong‐Jian; Zhao, Rongzhen; Liu, Qiuying; Wei, Ling; Yu, Xiaoqin; Li, Bo; Qin, Yang

doi:10.1016/j.gene.2017.07.077

Cited by 20 publications

(12 citation statements)

References 39 publications

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“…The aforementioned results demonstrated that CTCFL was the most upregulated gene in HG-EOCs. CTCFL belongs to the cancer testis antigen family (30), which is typically expressed in the testes (31). However, numerous studies investigating the high expression of CTCFL in multiple carcinomas have been reported, including breast cancer, lung cancer, endometrial carcinoma, prostate cancer and colon cancer, and the expression of CTCFL was associated with tumor size and histological differentiation (32–35).…”

Section: Discussionmentioning

confidence: 99%

Genome‑wide bioinformatics analysis reveals CTCFL is upregulated in high‑grade epithelial ovarian cancer

et al. 2019

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Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy that threatens the health of females. Previous studies have demonstrated that the survival outcomes of patients with different EOC grades varied. Therefore, the EOC grade is considered to serve as a distinctive prognostic factor. To date, the evaluation of ovarian cancer grade relies on pathological examination and a quantitative index for diagnosis is lacking. Furthermore, the dysregulation of genes has been demonstrated to exert pivotal functions in the carcinogenesis of EOCs. Therefore, the identification of effective biomarkers associated with EOC grade is of importance for the development of therapeutic regimens, and also contributes to the prediction of EOC prognosis. Microarrays have been increasingly applied for the identification of potential molecular biomarkers for numerous diseases including EOC. In the present study, four public microarray datasets (GSE26193, GSE63885, GSE30161 and GSE9891) were analyzed. A total of 6,103 upregulated probes corresponding to 5,766 genes, and 4,004 downregulated probes corresponding to 3,707 genes were identified in the GSE26193, GSE63885 and GSE30161 datasets. ALK and LTK ligand 2 was the most downregulated gene associated with the tumor grade, while CCCTC-binding factor like (CTCFL), EGF like domain multiple 6, radical S-adenosyl methionine domain containing 2 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 were the most upregulated genes associated with EOC grade. The GSE9891 dataset was added for further analysis. Only one probe (1552368_at) encoding for CTCFL was identified to be consistently upregulated in the four examined datasets. Immunohistochemical analysis was used to detect the expression of CTCFL between low- and high-grade EOC tissues and revealed that the EOC grade was closely associated with CTCFL level. This was corroborated via the reverse transcription-quantitative polymerase chain reaction. Taken together, the results of the present study suggested that CTCFL is upregulated in high-grade epithelial ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Genome‑wide bioinformatics analysis reveals CTCFL is upregulated in high‑grade epithelial ovarian cancer

et al. 2019

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“…The primers were used previously [17]. Primer sequences of the first round of PCR: forward 5'-GTGTTTTTTTTGGGGTTTTTTTTAT-3' and reverse 5'-CCCAAAACAACCCATACTCT TAA-3'; and the following thermal cycle conditions: 95 °C for 6 min; (95 °C for 45 s, 56 °C for 30 s and 72 °C for 45 s) × 36 cycles; 72 °C for 6 min [28]. Primer sequences of the second round of PCR (MSP): unmethylated forward 5'-GTGTATTGTTATTTTT-TATTTTTGTGTTAGTTT-3' and unmethylated reverse 5'-ACCCCTCACCACAAAAAACATAACCAA-3'; methylated forward 5'-GTATTGTTATTTTTTATTTTCGCGT-TAGTTC-3' and methylated reverse 5'-CCCTCACCGC-GAAAAACGTAACCGA-3' .…”

Section: Methodsmentioning

confidence: 99%

“…In addition, epigenetic alterations of CTCFL are considered to be of great value, and the activity of CTCFL promoters is thought to be chiefly regulated by DNA methylation [25,26]. Hypomethylation of CTCFL promoters results in the universal expression of CTCFL in endometrial cancer, gastric cancer, and hepatocellular carcinoma, which is highly correlated with clinical stage and prognosis [27][28][29].…”

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confidence: 99%

Hypomethylation of CTCFL promoters as a noninvasive biomarker in plasma from patients with hepatocellular carcinoma

Chen

Zhao

Chen

et al. 2020

neo

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Hepatocellular carcinoma (HCC) is the third deadliest cancer in the world with high morbidity and poor prognosis. CTCFL (CCCTC-binding factor like) is a member of the cancer testis antigen (CTA) family with oncogenic properties. To demonstrate whether the hypomethylation of CTCFL promoters in plasma could be used as a noninvasive biomarker to predict poor prognosis of HCC, we extracted cell-free DNA from the plasma and detected the methylation status of CTCFL in 43 HCC, 5 liver cirrhosis and 6 benign lesion samples using methylation specific PCR (MSP). Our study indicated that the hypomethylation of CTCFL promoters in HCC plasma samples (60.4%) was significantly different from that in benign lesion plasma samples (16.7%) with a p-value of 0.043. Analysis of clinicopathological data showed that the methylation status of CTCFL promoters was significantly correlated with microvascular involvement (MVI) (p=0.001) and postoperative recurrence (p=0.031). Furthermore, clinical prognosis data of 347 HCC patients from The Cancer Genome Atlas (TCGA) database displayed that the hypomethylated group had worse overall survival than the hypermethylated group (p=0.0056). In conclusion, we provide evidence that the hypomethylation of CTCFL promoters in cell-free DNA is a biomarker for monitoring HCC patients, which can be used as a noninvasive prediction index for tumor recurrence and provide the individualized decision-making for clinicians.

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“…Many types of human cancers present global genomic hypomethylation, including prostate tumors, hepatocellular carcinoma, B-cell chronic lymphocytic leukemia (B-CLL), cervical cancer, and others [85][86][87][88]. However, these relationships cannot be generalized, as Kushawa et al showed that both hypomethylation and hypermethylation are common in B-CLL and there is an interplay between them that contributes to cancer development [89].…”

Section: Dna Methylation In Breast Cancermentioning

confidence: 99%

Interplay between BRCA1 and GADD45A and Its Potential for Nucleotide Excision Repair in Breast Cancer Pathogenesis

Pietrasik

Zajac

Morawiec

et al. 2020

IJMS

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A fraction of breast cancer cases are associated with mutations in the BRCA1 (BRCA1 DNA repair associated, breast cancer type 1 susceptibility protein) gene, whose mutated product may disrupt the repair of DNA double-strand breaks as BRCA1 is directly involved in the homologous recombination repair of such DNA damage. However, BRCA1 can stimulate nucleotide excision repair (NER), the most versatile system of DNA repair processing a broad spectrum of substrates and playing an important role in the maintenance of genome stability. NER removes carcinogenic adducts of diol-epoxy derivatives of benzo[α]pyrene that may play a role in breast cancer pathogenesis as their accumulation is observed in breast cancer patients. NER deficiency was postulated to be intrinsic in stage I of sporadic breast cancer. BRCA1 also interacts with GADD45A (growth arrest and DNA damage-inducible protein GADD45 alpha) that may target NER machinery to actively demethylate genome sites in order to change the expression of genes that may be important in breast cancer. Therefore, the interaction between BRCA1 and GADD45 may play a role in breast cancer pathogenesis through the stimulation of NER, increasing the genomic stability, removing carcinogenic adducts, and the local active demethylation of genes important for cancer transformation.

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Hypomethylation of BORIS is a promising prognostic biomarker in hepatocellular carcinoma

Cited by 20 publications

References 39 publications

Genome‑wide bioinformatics analysis reveals CTCFL is upregulated in high‑grade epithelial ovarian cancer

Genome‑wide bioinformatics analysis reveals CTCFL is upregulated in high‑grade epithelial ovarian cancer

Hypomethylation of CTCFL promoters as a noninvasive biomarker in plasma from patients with hepatocellular carcinoma

Interplay between BRCA1 and GADD45A and Its Potential for Nucleotide Excision Repair in Breast Cancer Pathogenesis

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