Potential of RASSF1A promoter methylation as a biomarker for colorectal cancer: Meta-analysis and TCGA analysis

Hu, Fei; Chen, Li; Bi, Mingyu; Zheng, Ling; He, Junna; Huang, Yingze; Zhang, Xuelian; Guo, Qiang; Luo, Ying; Tang, Wenru; Sheng, Miaomiao

doi:10.1016/j.prp.2020.153009

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…RASSF1A hypermethylation is a promising biomarker for the diagnosis of HCC in tissue and blood and is an emerging biomarker for HCC[ 24 - 26 ]. In addition, RASSF1A hypermethylation is an early and potential prognostic biomarker in CRC[ 21 , 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

RASSF1A methylation as a biomarker for detection of colorectal cancer and hepatocellular carcinoma

Li¹,

Li²,

Run³

et al. 2022

WJGO

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BACKGROUND Studies have validated the potential of methylated cell-free DNA as a biomarker in various tumors, and methylated DNA in plasma may be a potential biomarker for cancer. AIM To evaluate the diagnostic value of RASSF1A methylation in plasma for colorectal cancer (CRC) and hepatocellular carcinoma (HCC). METHODS A total of 92 CRC patients, 67 colorectal polyp (CRP) patients, 63 HCC patients, and 66 liver cirrhosis (LC) patients were enrolled. The plasma DNA was subjected to DNA extraction, double-strand DNA concentration determination, bisulfite conversion, purification, single-strand DNA concentration determination, and digital polymerase chain reaction (PCR) detection. The methylation rate was calculated. The diagnostic value was evaluated by the area under the curve (AUC). RESULTS The age and sex in the CRC and CRP groups and the HCC and LC groups were also matched. The DNA methylation rate of RASSF1A in plasma in the CRC group was 2.87 ± 1.80, and that in the CRP group was 1.50 ± 0.64. DNA methylation of RASSF1A in plasma showed a significant difference between the CRC and CRP groups. The AUC of RASSF1A methylation for discriminating the CRC and CRP groups was 0.82 (0.76-0.88). The AUCs of T1, T2, T3 and T4 CRC and CRP were 0.83 (0.72-0.95), 0.87 (0.78-0.95), 0.86 (0.77-0.95), and 0.75 (0.64-0.85), respectively. The DNA methylation rate of RASSF1A in plasma in the HCC group was 4.45 ± 2.93, and that in the LC group was 2.46 ± 2.07. DNA methylation of RASSF1A in plasma for the HCC and LC groups showed a significant difference. The AUC of RASSF1A methylation for discriminating the HCC and LC groups was 0.70 (0.60-0.79). The AUCs of T1, T2, T3 and T4 HCC and LC were 0.80 (0.61, 1.00), 0.74 (0.59-0.88), 0.60 (0.42-0.79), and 0.68 (0.53-0.82), respectively. CONCLUSION RASSF1A methylation in plasma detected by digital PCR may be a potential biomarker for CRC and HCC.

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Section: Discussionmentioning

confidence: 99%

RASSF1A methylation as a biomarker for detection of colorectal cancer and hepatocellular carcinoma

Li¹,

Li²,

Run³

et al. 2022

WJGO

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“…Hu et al, by conducting a meta-analysis on the hypermethylation status of the RASSF1 promoter in CRC from 21 studies, reported a highly variable hypermethylation frequency, ranging from 15.84% to 93.3%. However, they note that some studies had RASSF1 hypermethylation in non-tumour control samples [ 33 ]. RASSF1 promoter hypermethylation is also reported in osteosarcoma, breast cancer, upper aerodigestive tract cancer, glioma, clear cell carcinoma of the kidney, urothelial carcinoma, thyroid carcinoma, and neuroblastoma [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…RASSF1 promoter hypermethylation is also reported in osteosarcoma, breast cancer, upper aerodigestive tract cancer, glioma, clear cell carcinoma of the kidney, urothelial carcinoma, thyroid carcinoma, and neuroblastoma [ 34 ]. Hu et al also analysed three other studies, which focused on the prognostic impact of RASSF1 hypermethylation status and highlighted that RASSF1 hypermethylation is a poor prognostic factor [ 33 ]. This prognostic impact has also been observed by Jiang et al, who demonstrated poorer survival of breast cancer patients when the RASSF1 promoter is hypermethylated [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Deciphering Promoter Hypermethylation of Genes Encoding for RASSF/Hippo Pathway Reveals the Poor Prognostic Factor of RASSF2 Gene Silencing in Colon Cancers

Riffet

Eid

Faisant

et al. 2021

Cancers

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The aims of this study were to assess the frequency of promoter hypermethylation of the genes encoding the Ras associated domain family (RASSF)/Hippo pathway, as well as the impact on overall (OS) and progression-free survival (PFS) in a single-center retrospective cohort of 229 patients operated on for colon cancers. Hypermethylation status was investigated by methylation-specific PCR on the promoters of the RASSF1/2, STK4/3 (encoding Mammalian Ste20-like protein 1 and 2 (MST1 and 2), respectively), and LATS1/2 genes. Clinicopathological characteristics, recurrence-free survival, and overall survival were analysed. We found the RASSF/Hippo pathway to be highly silenced in colon cancer, and particularly RASSF2 (86%). The other promoters were hypermethylated with a lesser frequency of 16, 3, 1, 10 and 6%, respectively for RASSF1, STK4, STK3, LATS1, and LATS2 genes. As the hypermethylation of one RASSF/Hippo family member was by no means exclusive from the others, 27% of colon cancers displayed the hypermethylation of at least two RASSF/Hippo member promotors. The median overall survival of the cohort was 60.2 months, and the median recurrence-free survival was 46.9 months. Survival analyses showed a significantly poorer overall survival of patients when the RASSF2 promoter was hypermethylated (p = 0.03). The median OS was 53.5 months for patients with colon cancer with a hypermethylated RASSF2 promoter versus still not reached after 80 months follow-up for other patients, upon univariate analysis (HR = 1.86, [95% CI: 1.05–3.3], p < 0.03). Such difference was not significant for relapse-free survival as in multivariate analysis. A logistic regression model showed that RASSF2 hypermethylation was an independent factor. In conclusion, RASSF2 hypermethylation is a frequent event and an independent poor prognostic factor in colon cancer. This biomarker could be investigated in clinical practice.

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“…Promoter methylation of RASSF1A can affect the sensitivity of patients with CRC to oxaliplatin-based chemotherapy. In a study by Sun et al (97), it was identified that RASSF1A methylation was independently correlated with the prognosis of patients treated with oxaliplatin-based chemotherapy, while another meta-analysis revealed that RASSF1A hypermethylation was a risk factor and a potential prognostic biomarker in CRC (98). Moreover, it was indicated that the methylation of RASSF1A may be a prognostic marker for stage II and III CRC cases.…”

Section: Ras Association Domain Family Protein 1 (Rassf1a)mentioning

confidence: 99%

Value of methylation markers in colorectal cancer (Review)

Kong

2021

Oncol Rep

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Colorectal cancer (CRC) is a multifactorial and multistage process that occurs due to both genetic and epigenetic variations in normal epithelial cells. Analysis of the CRC epigenome has revealed that almost all CRC types have a large number of abnormally methylated genes. Hypermethylation of cell-free DNA from CRC in the blood or stool is considered as a potential non-invasive cancer biomarker, and various methylation markers have shown high sensitivity and specificity. The aim of the present review was to examine potential methylation markers in CRC that have been used or are expected to be used in the clinical setting, focusing on their screening, predictive, prognostic and therapeutic roles in CRC.

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Potential of RASSF1A promoter methylation as a biomarker for colorectal cancer: Meta-analysis and TCGA analysis

Cited by 9 publications

References 24 publications

RASSF1A methylation as a biomarker for detection of colorectal cancer and hepatocellular carcinoma

RASSF1A methylation as a biomarker for detection of colorectal cancer and hepatocellular carcinoma

Deciphering Promoter Hypermethylation of Genes Encoding for RASSF/Hippo Pathway Reveals the Poor Prognostic Factor of RASSF2 Gene Silencing in Colon Cancers

Value of methylation markers in colorectal cancer (Review)

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