Epigenetic profiling and mRNA expression reveal candidate genes as biomarkers for colorectal cancer

Zhang, Hui; Dong, Shuchen; Feng, Jifeng

doi:10.1002/jcb.28368

Cited by 20 publications

(10 citation statements)

References 32 publications

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“…It could be inferred that the chemoradiotherapy will affect TCN1 expression through some mechanism. Zhang et al screened differentially expressed genes from the Gene Expression Omnibus database and revealed that aberrant expression of TCN1 and TGFBI was regulated by DNA methylation 28 . Lee et al performed in vitro assays and verified that downregulation of TCN1 led to an obvious reduction in the proliferation of FaDu cells.…”

Section: Discussionmentioning

confidence: 99%

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer

Liu

Wang

Yue

et al. 2020

Sci Rep

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Transcobalamin (TCN1) is a vitamin B12 (cobalamin)-binding protein that regulates cobalamin homeostasis. Recent studies and bioinformatic analyses have found that TCN1 is highly expressed in cancer tissues and is associated with tumour aggressiveness and poor prognosis. the present study aimed to detect TCN1 as a novel biomarker for prognosis and chemosensitivity of colon cancer. nextgeneration sequencing showed that TCN1 was one of several upregulated mRnAs in colon cancer, which was verified by further bioinformatics analyses. Western blotting (n = 9) and quantitative real time polymerase chain reaction (qRT-PCR, n = 30) revealed that TCN1 was highly expressed in colon cancer tissues at both the protein and mRNA level. A total of 194 cases of colon cancer were examined by immunohistochemistry and revealed that TCN1 expression level was related to advanced stages (P < 0.005). Kaplan-Meier analysis verified that patients with lower TCN1 expression usually had longer overall survival (P = 0.008). In addition, TCN1 was highly expressed in pulmonary metastatic tumour tissues (n = 37, P = 0.025) and exhibited higher levels in right-sided colon cancer than in left-sided colon cancer (P = 0.029). TCN1 expression in specimens that had received neoadjuvant chemotherapy decreased compared with that in colonoscopy biopsy tissues (n = 42, P = 0.009). Further bioinformatics analyses verified that apoptosis pathways might have a role in high TCN1 expression. All the studies revealed that TCN1 expression in colon cancer was significantly associated with malignant biological behaviour. Therefore, TCN1 could be used as a novel biomarker for colon cancer aggressiveness and prognosis and might also be a potential biomarker for predicting neoadjuvant chemosensitivity. According to the data from GLOBOCAN 2018, colorectal cancer (CRC) is one of the most common intestinal tumours and ranks as the fourth leading cause of morbidity and the second leading cause of cancer-related mortality worldwide 1. Despite major developments in surgery and therapeutics, long-term survival remains far from satisfactory 2,3 , mainly because CRC is often detected at more advanced stages. Currently, diagnosis, relapse, and metastasis monitoring of CRC largely relies on colonoscopy and imaging data, which is usually delayed. Therefore, new sensitive biomarkers are urgently required to ensure early diagnosis and to predict progression and administer timely treatments. Transcobalamin I (TCN1) is a type of vitamin B12 (cobalamin)-binding protein that transports cobalamin from the stomach to the intestines. It plays various roles in maintaining the basic function of cell proliferation and

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Section: Discussionmentioning

confidence: 99%

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer

Liu

Wang

Yue

et al. 2020

Sci Rep

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“…Numerous known cancer-associated genes were included in the methylated gene set of the present study, certain of which are known to cause tumor development. For instance, the ectopic expression of transforming growth factor beta induced is associated with enhanced metastasis and extravasation of CRC (19)(20)(21). Polymeric immunoglobulin receptor promotes tumor growth in hepatocellular carcinoma (22), but inhibits pancreatic and periampullary adenocarcinoma development (23).…”

Section: Discussionmentioning

confidence: 99%

DNA‑methylated gene markers for colorectal cancer in TCGA database

Zhang

Sun

et al. 2020

Exp Ther Med

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Colorectal cancer (CRC) is characterized by the accumulation of genetic and epigenetic alterations in neoplastic processes. DNA methylation, as an important epigenetic process, contributes to the development of CRC. In the present study, the epigenetic landscape of genes in CRC was characterized by analyzing the dataset from The Cancer Genome Atlas database and 177 DNA-methylated genes were screened based on the criterion of the Pearson correlation (R) between expression and methylation levels being >0.4. Pathway enrichment analysis revealed prominent pathways, including transcription and metabolism, further implying their significant role in tumorigenesis. Among the methylated genes, only zinc finger protein (ZNF)726 with aberrant expression was determined to affect overall survival (OS) as well as disease-free survival of patients with CRC. In addition, ZNF726 was identified as an independent prognostic risk factor for OS in patients with CRC. The methylation-based regulation of ZNF726 expression in CRC cells was further assessed using the Cancer Cell Line Encyclopedia database. Finally, the CpG island methylation of the ZNF726 promoter was evaluated to further elucidate its role in the development of CRC. In conclusion, the epigenetic landscape of genes in terms of promoter methylation in CRC was characterized, revealing that aberrant expression of ZNF726 may be an independent prognostic risk factor for OS in patients with CRC.

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“…Coefficient values < 0 were considered statistically significant. In addition, we further performed survival analysis [ 4 ] and constructed Cox regression models [ 23 ] to screen candidate genes associated with EC progression. Based on univariate and multivariate analyses, we identified several genes with prognostic value.…”

Section: Methodsmentioning

confidence: 99%

Identification of MTHFD2 as a novel prognosis biomarker in esophageal carcinoma patients based on transcriptomic data and methylation profiling

et al. 2020

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DNA methylation is an important epigenetic regulatory mechanism in esophageal carcinoma (EC) and is associated with genomic instability and carcinogenesis. In the present study, we aimed to identify tumor biomarkers for predicting prognosis of EC patients. We downloaded mRNA expression profiles and DNA methylation profiles associated with EC from the Gene Expression Omnibus database. Differentially expressed and differentially methylated genes between tumor tissues and adjacent normal tissue samples were identified. Functional enrichment analyses were performed, followed by the construction of protein–protein interaction networks. Data were validated based on methylation profiles from The Cancer Genome Atlas. Candidate genes were further verified according to survival analysis and Cox regression analysis. We uncovered multiple genes with differential expression or methylation in tumor samples compared with normal samples. After taking the intersection of 3 differential gene sets, we obtained a total of 232 overlapping genes. Functional enrichment analysis revealed that these genes are related to pathways such as “glutathione metabolism,” “p53 signaling pathway,” and “focal adhesion.” Furthermore, 8 hub genes with inversed expression and methylation correlation were identified as candidate genes. The abnormal expression levels of MSN, PELI1, and MTHFD2 were correlated with overall survival times in EC patients ( P < .05). Only MTHFD2 was significantly associated with a pathologic stage according to univariate analysis ( P = .037) and multivariate analysis ( P = .043). Our study identified several novel EC biomarkers with prognostic value by integrated analysis of transcriptomic data and methylation profiles. MTHFD2 could serve as an independent biomarker for predicting prognosis and pathological stages of EC.

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Epigenetic profiling and mRNA expression reveal candidate genes as biomarkers for colorectal cancer

Cited by 20 publications

References 32 publications

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer

DNA‑methylated gene markers for colorectal cancer in TCGA database

Identification of MTHFD2 as a novel prognosis biomarker in esophageal carcinoma patients based on transcriptomic data and methylation profiling

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