• DNA methylation
• Diagnosis
• Liquid biopsy
• Prostatic neoplasms

• 210810307303 Clinical Medical Research Center for Minimally Invasive Treatment of Urology

• DNA methylation
• DNMT1
• PLA2G2A
• STUB1
• UHRF1

• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/metabolism
• Cholangiocarcinoma/pathology
• Humans
• Ubiquitination
• DNA Methylation
• Ubiquitin-Protein Ligases/metabolism
• Ubiquitin-Protein Ligases/genetics
• Mice
• CCAAT-Enhancer-Binding Proteins/metabolism
• CCAAT-Enhancer-Binding Proteins/genetics
• Animals
• Bile Duct Neoplasms/genetics
• Bile Duct Neoplasms/pathology
• Bile Duct Neoplasms/metabolism
• Disease Progression
• Male
• Cell Proliferation
• Female
• Cell Line, Tumor
• DNA (Cytosine-5-)-Methyltransferase 1/metabolism
• DNA (Cytosine-5-)-Methyltransferase 1/genetics

• 81502108 National Natural Science Foundation of China
• 81974438 National Natural Science Foundation of China
• 82173069 National Natural Science Foundation of China

• Chemotherapy-induced alopecia
• Hair follicle stem cells
• MiRNA
• RRBS

• Cancer
• Lidocaine
• Local anesthesia
• Surgery
• Survival
• Tumor microenvironment

• Humans
• Lidocaine/therapeutic use
• Lidocaine/pharmacology
• Neoplasms/drug therapy
• Neoplasms/pathology
• Anesthetics, Local/therapeutic use
• Anesthetics, Local/pharmacology
• Anesthetics, Local/administration & dosage
• Animals
• Disease Progression
• Tumor Microenvironment/drug effects
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/pharmacology

• R01 CA250412 NCI NIH HHS
• R01 CA251545 NCI NIH HHS
• R01 EB029596 NIBIB NIH HHS
• R37 CA248018 NCI NIH HHS

• CHSY3
• gastric cancer
• prognosis
• tumor immune microenvironment
• tumor-associated macrophages

• Aged
• Female
• Humans
• Male
• Middle Aged
• Biomarkers, Tumor/metabolism
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Prognosis
• Stomach Neoplasms/pathology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/mortality
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/immunology
• Tumor-Associated Macrophages/immunology
• Tumor-Associated Macrophages/metabolism

• ALDH3A2
• Lipid accumulation
• PI3K-AKT
• Renal cancer
• miR-1182

• DNA methylation
• EBV
• cfDNA
• early screening
• nasopharyngeal carcinoma

• Humans
• Nasopharyngeal Carcinoma/diagnosis
• Epstein-Barr Virus Infections/diagnosis
• Nasopharyngeal Neoplasms/diagnosis
• Nasopharyngeal Neoplasms/genetics
• Nasopharyngeal Neoplasms/pathology
• Herpesvirus 4, Human/genetics
• DNA, Viral/genetics
• Cell-Free Nucleic Acids

• cancer
• colon
• colon cancer
• colon cancer prevention
• colon cancer surveillance
• colon polyps
• colonoscopy
• colorectal cancer
• fit test
• fobt

• AR-V7
• SLC22A3
• TAZ
• YAP1
• enzalutamide resistance

• Humans
• Male
• Drug Resistance, Neoplasm/genetics
• Nitriles/pharmacology
• Nitriles/therapeutic use
• Phenylthiohydantoin/pharmacology
• Phenylthiohydantoin/therapeutic use
• Prostatic Neoplasms, Castration-Resistant/drug therapy
• Prostatic Neoplasms, Castration-Resistant/genetics
• Prostatic Neoplasms, Castration-Resistant/metabolism
• Prostatic Neoplasms, Castration-Resistant/secondary
• Receptors, Androgen/genetics
• Receptors, Androgen/metabolism
• Androgen Receptor Antagonists/pharmacology
• Androgen Receptor Antagonists/therapeutic use
• Antineoplastic Agents, Hormonal/pharmacology
• Antineoplastic Agents, Hormonal/therapeutic use

• KUOS 22-03 Korean Urologic Oncology Society
• 2022R1A2C1010038 National Research Foundation of Korea
• NRF-2020R1A2C2007662 National Research Foundation of Korea
• NRF-2020R1C1C1005054 National Research Foundation of Korea
• NRF-2021R1I1A1A01040437 National Research Foundation of Korea
• NRF2016R1D1A1B01012138 National Research Foundation of Korea
• SMO1210241 Samsung Medical Center Research and Development Grant
• BT210153 Seoul R&BD Program

• breast cancer
• toxicology

Mammalian genomic DNA methylation represents a key epigenetic modification and its dynamic regulation that fine-tunes the gene expression of multiple pathways during development. It maintains the gene expression of one generation of cells; particularly, the mitotic inheritance of gene-expression patterns makes it the key governing mechanism of epigenetic change to the next generation of cells. Convincing evidence from recent discoveries suggests that the dynamic regulation of DNA methylation is accomplished by the enzymatic action of TET dioxygenase, which oxidizes the methyl group of cytosine and activates transcription. As a result of aberrant DNA modifications, genes are improperly activated or inhibited in the inappropriate cellular context, contributing to a plethora of inheritable diseases, including cancer. We outline recent advancements in understanding how DNA modifications contribute to tumor suppressor gene silencing or oncogenic-gene stimulation, as well as dysregulation of DNA methylation in cancer progression. In addition, we emphasize the function of PARP1 enzymatic activity or inhibition in the maintenance of DNA methylation dysregulation. In the context of cancer remediation, the impact of DNA methylation and PARP1 pharmacological inhibitors, and their relevance as a combination therapy are highlighted.

Effects of anesthetic interventions on cancer prognosis remain controversial. There is evidence that estrogen receptor (ER)-negative breast cancer patients have an early recurrence peak. We aimed to assess the potential benefit of regional anesthesia-analgesia versus general anesthesia regarding early recurrence in breast cancer according to ER expression.

Based on a multicenter randomized controlled trial (clinicaltrials.gov, NCT00418457), we included all the patients from Peking Union Medical College Hospital research center in this study. The primary outcome was breast cancer recurrence after surgery. The Cox proportional hazard model was used to compare recurrence between groups.

In total, 1,253 breast cancer patients were included in this sub-study, among whom the median follow-up time was 53 months. In this sub-study, 320 patients were ER-negative, and 933 were ER-positive. As for ER-negative patients, the recurrence risk in the PPA (paravertebral blocks and propofol general anesthesia) group showed no statistical difference compared with the GA (sevoflurane and opioids general anesthesia) group (19.1% versus 23.4%; adjusted HR: 0.80, 95% CI: 0.50–1.30; P = 0.377). In the first 18 months after breast cancer surgery, which is considered as the classical early peak of recurrence, after adjustment for menstruation and the pathological stage of tumor, the decrease of early recurrence observed in the PPA group was not significant compared with the GA group (adjusted HR: 0.63, 95% CI: 0.34–1.14; P = 0.127).

In our study, the effects of early recurrence after breast cancer surgery in both ER-negative and ER-positive patients were similar between regional anesthesia-analgesia and general anesthesia. Large samples of ER-negative patients will be needed to clarify the effects of anesthetic interventions.

• anesthesia
• breast cancer
• estrogen receptor
• propofol
• recurrence

• ctcf
• zfp57
• atf7ip
• mutation
• colon neoplasm

• CCCTC-Binding Factor
• Colonic Neoplasms/genetics
• Colonic Neoplasms/metabolism
• Colorectal Neoplasms/genetics
• DNA Methylation
• Frameshift Mutation
• Humans
• Microsatellite Instability
• Microsatellite Repeats
• Mutation
• Repressor Proteins
• Stomach Neoplasms/metabolism

Renal cell carcinoma (RCC) is an increasingly common malignancy that can progress to metastatic renal cell carcinoma (mRCC) in approximately one-third of RCC patients. The 5-year survival rate for mRCC is abysmally low, and, at the present time, there are sparingly few if any effective treatments. Current surgical and pharmacological treatments can have a long-lasting impact on renal function, as well. Thus, there is a compelling unmet need to discover novel biomarkers and surveillance methods to improve patient outcomes with more targeted therapies earlier in the course of the disease. Circulating biomarkers, such as circulating tumor DNA, noncoding RNA, proteins, extracellular vesicles, or cancer cells themselves potentially represent a minimally invasive tool to fill this gap and accelerate both diagnosis and treatment. Here, we discuss the clinical relevance of different circulating biomarkers in metastatic renal cell carcinoma by clarifying their potential role as novel biomarkers of response or resistance to treatments but also by guiding clinicians in novel therapeutic approaches.

• DNA methylation
• bioconjugation
• bioelectroanalysis
• cancer
• epigenetic
• nano ink

The development of brain metastases, or intracranial metastatic disease (IMD), is a serious and life-altering complication for many patients with cancer. While there have been substantial advancements in the treatments available for IMD and in our understanding of its pathogenesis, conventional methods remain insufficient to detect IMD at an early stage. In this review, we discuss current research on biomarkers specific to IMD. In particular, we highlight biomarkers that can be easily accessed via the bloodstream or cerebrospinal fluid, including circulating tumor cells and DNA, as well as advanced imaging techniques. The continued development of these assays could enable clinicians to detect IMD prior to the development of IMD-associated symptoms and ultimately improve patient prognosis and survival.

Nearly 30% of patients with cancer will develop intracranial metastatic disease (IMD), and more than half of these patients will die within a few months following their diagnosis. In light of the profound effect of IMD on survival and quality of life, there is significant interest in identifying biomarkers that could facilitate the early detection of IMD or identify patients with cancer who are at high IMD risk. In this review, we will highlight early efforts to identify biomarkers of IMD and consider avenues for future investigation.

• biomarker
• brain metastases
• breast cancer
• intracranial metastatic disease
• melanoma
• non-small cell lung cancer

• DNA methylation
• biomedical analysis
• biosensor
• epigenetic
• genetic mutations

Dihydropyrimidine dehydrogenase deficiency is a major cause of severe fluoropyrimidine-induced toxicity and could lead to interruption of chemotherapy or life-threatening adverse reactions. This study aimed to characterize the DPYD exon sequence, mRNA expression and in vivo DPD activity by plasma uracil concentration. It was carried out in two groups of patients with extreme phenotypes (toxicity versus control) newly treated with a fluoropyrimidine, during the first three cycles of treatment. A novel nonsense gene variant (c.2197insA) was most likely responsible for fluoropyrimidine-induced toxicity in one patient, while neither DPYD mRNA expression nor plasma uracil concentration was globally associated with early toxicity. Our present work may help improve pharmacogenetic testing to avoid severe and undesirable adverse reactions to fluoropyrimidine treatment and it also supports the idea of looking beyond DPYD.

• 5-fluorouracil
• adverse drug events
• cancer
• capecitabine
• pharmacogenetics

• Administration, Oral
• Animals
• Antimetabolites, Antineoplastic/pharmacology
• Apoptosis
• Cell Proliferation
• Decitabine/chemistry
• Decitabine/pharmacology
• Humans
• Leukemia, Myeloid, Acute/drug therapy
• Leukemia, Myeloid, Acute/metabolism
• Leukemia, Myeloid, Acute/pathology
• Macaca fascicularis
• Mice
• Mice, Inbred BALB C
• Myelodysplastic Syndromes/drug therapy
• Myelodysplastic Syndromes/metabolism
• Myelodysplastic Syndromes/pathology
• Silanes/chemistry
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays

• Cancer
• Cancer immunotherapy
• Clinical pharmacology
• DNA-methylation
• Epigenetics
• Nanobiomedicine

• DNA-methylation
• bioinformatics
• cell-free DNA
• epigenetics
• genomics
• liquid biopsy
• oncology
• precision medicine
• sequencing

• Animals
• Cell-Free Nucleic Acids/genetics
• Computational Biology
• DNA Methylation/genetics
• Humans
• Liquid Biopsy
• Medical Oncology/methods

• GR-2018-12365195 Italian Minister of Health

MicroRNAs (miRNAs/miRs) are a type of non-coding single-stranded RNA, with a length of ~22 nt, which are encoded by endogenous genes and are involved in the post-transcriptional regulation of gene expression in animals and plants. Studies have demonstrated that miRNAs play an important role in the occurrence, development, metastasis, diagnosis and treatment of cancer. In recent years, miR-497 has been identified as one of the key miRNAs in a variety of cancer types and has been shown to be downregulated in a variety of solid tumors. However, the regulation of miR-497 expression involves a complex network, which is affected by several factors. The aim of the present review was to summarize the mechanism of regulation of miR-497 expression at the pre-transcriptional and transcriptional levels in cancer, as well as the role of miR-497 expression imbalance in cancer diagnosis, treatment and prognosis. The regulatory mechanisms of miR-497 expression may aid in our understanding of the causes of miR-497 expression imbalance and provide a reference value for further research on the diagnosis and treatment of cancer.

• cancer
• clinical significance
• expression
• microRNA-497
• regulatory mechanisms

Background: It has been reported that local anesthetics are toxic to various types of cells. Furthermore, several local anesthetics have been confirmed to exert demethylation effects and regulate the proliferation of human cancer cells. Our previous findings suggest that lidocaine may exert potential antitumor activity and enhance the sensitivity of cisplatin to hepatocellular carcinoma in vitro and in vivo. A recent study proved that lidocaine sensitizes breast cancer cells to cisplatin via upregulation of RASSF1A, a promotor of tumor suppressive gene (TSG) demethylation. We sought to determine whether amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine) exert growth-inhibitory effects on human hepatoma cells and to determine whether amide-type local anesthetics sensitize human hepatoma cells to cisplatin-mediated cytotoxicity via upregulation of RASSF1A expression.

Methods: Human hepatoma cell lines HepG2 and BEL-7402 were incubated with lidocaine, ropivacaine and bupivacaine. The viability of local anesthetic-treated cells with or without cisplatin was investigated. Further, we evaluated RASSF1A expression after treatment of HepG2 and BEL-7402 cells with three local anesthetics and determined the influence of RASSF1A expression on the toxicity of cisplatin to these cells.

Results: The viability of HepG2 and BEL-7402 cells was significantly decreased by treatment with amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine). In these cells, the combination treatment with cisplatin and local anesthetics exhibited a stronger reduction in viability. Lidocaine, ropivacaine and bupivacaine promoted a significant increase in RASSF1A expression and a decrease in RASSF1A methylation. The combined treatment with both local anesthetics and cisplatin resulted in a significantly lower level of HepG2 and BEL-7402 cell viability than that with singular local anesthetics or cisplatin treatment. Moreover, local anesthetics enhanced the cytotoxicity of cisplatin against HepG2 and BEL-7402 cells, accompanied by an increase in RASSF1A expression.

Conclusions: These data indicated that amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine) have growth-inhibitory and demethylation effects in human hepatoma cells. We also found that these amide local anesthetics may enhance the cytotoxicity of cisplatin in human hepatocellular carcinoma cells possibly via upregulation of RASSF1A expression and demethylation.

• DNA demethylation
• RASSF1A
• amide-type local anesthetics
• cisplatin
• human hepatoma cells

• 5-aza-dC
• Cytokines
• Naive T cells
• PGE2
• TGFB1
• Tregs

Pancreatic adenocarcinoma (PAAD) accounts for ~85% of all pancreatic cancer cases and is associated with a less favorable prognosis. Aberrant DNA methylation may influence the progression of PAAD by inducing abnormal gene expression. Methylation data of PAAD samples with prognosis information were obtained from The Cancer Genome Atlas (training set) and European Bioinformatics Institute Array Express databases (validation sets). Using the limma package, the differentially methylated genes in the training dataset were screened. Combined with the Weighted Gene Co-expression Network Analysis package, the co-methylated genes in key modules were identified. Then, a cor.test function in R software was applied to explore the functions of key the methylated genes. Correlation analyses of the expression levels and methylation levels of key methylated genes were performed, followed by identification of methylated genes associated with prognosis using Univariate Cox regression analysis. The optimal combination of prognosis related methylated genes was determined using a Cox-Proportional Hazards (Cox-PH) model. Subsequently, the risk score prognostic prediction system was constructed by combining the Cox-PH prognosis coefficients of the selected optimized genes. Based on the constructed risk score system, samples in all datasets were divided into high and low risk samples and the survival status was compared using survival curves. Furthermore, the correlation between independent prognostic factors and the risk score system was determined using the survival package. A total of 50 genes associated with prognosis of PAAD and a 12-gene optimal combination were obtained, including: CCAAT/enhancer binding protein α, histone cluster 1 H4E, STAM binding protein-like 1, phospholipase D3, centrosomal protein 55, ssDNA binding protein 4, glutamate AMPA receptor subunit 1, switch-associated protein 70, adenylate-cyclase activating polypeptide 1 receptor 1, yippee-like 3, homeobox C4 and insulin-like growth factor binding protein 1. Subsequently, a risk score prognostic prediction system of these 12 genes was constructed and validated. In addition, pathological N category, radiotherapy and risk status were identified as independent prognostic factors. Overall, the risk score prognostic prediction system constructed in the present study may be effective for predicting the prognosis of patients with PAAD.

• correlation analysis
• differentially methylated genes
• pancreatic adenocarcinoma
• risk score system
• weighted gene co-expression network analysis

Epigenetic silencing of the O⁶-methylguanine-DNA methyltransferase (MGMT) DNA repair enzyme via promoter hypermethylation (hmMGMT) may increase mutations in the TP53 oncosuppressor gene and contribute to carcinogenesis. The effects of smoking, which is a risk factor for head and neck squamous cell carcinoma (HNSCC), were investigated to determine whether they up- or down-regulate hmMGMT. Additionally, the impact of hmMGMT and disruptive TP53-mutations on relapse was investigated in patients with HNSCC.

This study included 164 patients with HNSCC who were negative for both p16 protein expression and human papilloma virus infection. The association of smoking and hmMGMT was investigated using multiple logistic regression analysis. Competing risk regression was used to evaluate the effects of hmMGMT and TP53-mutations in exon 2 to 11 on relapse of HNSCC.

hmMGMT was observed in 84% of the 164 patients. TP53-mutations, specifically, G:C>A:T transition, were more frequent in patients with hmMGMT (32%) than in those without hmMGMT (8%). The frequency of disruptive TP53-mutations was not significantly different between groups. Compared with nonsmoking, heavy smoking of 20 pack-years or more was significantly associated with decreased hmMGMT (adjusted odds ratio, 0.08; 95% CI, 0.01 to 0.56; P = 0.01). Patients who had both hmMGMT and disruptive TP53-mutations showed a significantly higher relapse rate than all other patients (subdistribution hazard ratio, 1.77; 95% CI, 1.07 to 2.92; P = 0.026).

It was found that hmMGMT was suppressed by heavy smoking, and hmMGMT combined with disruptive TP53-mutations may indicate a poor prognosis in patients with HNSCC.

• DNA Methylation
• DNA Modification Methylases/genetics
• DNA Repair Enzymes/genetics
• Female
• Humans
• Male
• Middle Aged
• Mutation
• Promoter Regions, Genetic/genetics
• Recurrence
• Smoking
• Squamous Cell Carcinoma of Head and Neck/genetics
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Proteins/genetics

• ADCY6
• DNA methylation
• luminal-like breast cancer
• tumor-immune microenvironment

Circular RNA (circRNA), a type of non-coding RNA, can promote or suppress tumorigenesis. To investigate the involvement of circRNA in diffuse large B-cell lymphoma (DLBCL), we performed a circRNA microarray analysis on paired DLBCL and normal tissues. We identified a novel and highly stable circRNA originating from the back-splicing of APC exon 7 to exon 14, circ-APC (hsa_circ_0127621), which was downregulated in DLBCL tissues, cell lines and plasma. In gain-of-function experiments, ectopic expression of circ-APC inhibited DLBCL cell proliferation in vitro and tumor growth in vivo. Cytoplasmic circ-APC functioned as a sponge for miR-888, thus post-transcriptionally upregulating APC by alleviating the repressive effects of miR-888 on this gene. Further, nuclear circ-APC bound to the APC promoter and recruited the DNA demethylase TET1, thereby transcriptionally upregulating APC. Upon its upregulation, APC dampened the canonical Wnt/β-catenin signaling pathway by reducing the accumulation of β-catenin in the nucleus, thereby retarding DLBCL growth. Clinically, circ-APC was found to be an effective diagnostic and prognostic biomarker for patients with DLBCL. Our study suggests that circ-APC is a novel proliferation inhibitor, and that restoring circ-APC expression may be a promising therapeutic approach for DLBCL patients.

• biomarker
• circ-APC
• circular RNA
• diffuse large B-cell lymphoma

Epigenetics has been defined as ‘a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence’ and several epigenetic regulators are recurrently mutated in hematological malignancies. Epigenetic modifications include changes such as DNA methylation, histone modifications and RNA associated gene silencing. Transcriptional regulation, chromosome stability, DNA replication and DNA repair are all controlled by these modifications. Mutations in genes encoding epigenetic modifiers are a frequent occurrence in hematologic malignancies and important in both the initiation and progression of cancer. Epigenetic modifications are also frequently reversible, allowing excellent opportunities for therapeutic intervention. The goal of epigenetic therapies is to reverse epigenetic dysregulation, restore the epigenetic balance, and revert malignant cells to a more normal condition. The role of epigenetic therapies thus far is most established in hematologic malignancies, with several agents already approved by the US Food and Drug Administration. In this review, we discuss pharmacological agents targeting epigenetic regulators.

• BET inhibitors
• DOT1L inhibitors
• IDH inhibitors
• LSD1 inhibitors
• acute myeloid leukemia
• demethylases
• epigenetic modifications
• histone modification
• hypomethylating agents
• myelodysplastic syndrome
• novel agents

• Antioxidant
• Epigenetics
• Mouse epidermal cells
• Nrf2
• Pelargonidin

Alterations in DNA methylation may cause disturbances in regulation of gene expression, including drug metabolism and distribution. Moreover, many cancers, including breast cancer, are characterized by DNA hypomethylation and a decreased 5-hydroxymethylcytosine level. The abnormal cell growth found in breast carcinoma might be the result of impaired up-regulation of breast cancer receptors. Receptors’ expression in breast cancer determines clinical outcome, and it is possible that they lead to different DNA methylation patterns. Excessive steroid exposure can affect DNA methylation by promoting demethylation of CpG islands in promoter regions of genes, and hence may have an impact on promotion and progression of breast cancer cells. Tamoxifen, as a leading drug in breast cancer hormone therapy, has an ability to act like estrogen or antiestrogen depending on the type and localization of the breast cancer receptor. Further studies are needed to determine whether tamoxifen, similarly to steroids, may evoke changes in methylation pattern.

• DNA demethylation
• breast cancer receptors
• epigenetics
• tamoxifen

Research on DNA methylation offers great potential for the identification of biomarkers that can be applied for accurately assessing an individual's risk for cancer. In this article, we try to find the ideal epigenetic genes involved in colorectal cancer (CRC) based on a CRC database and our CRC cohort. The top 20 genes with an extremely high frequency of hypermethylation in CRC were identified in the latest database. Remarkably, 3 HOXA genes were included in this list and ranked at the top. The percentage of methylation in the HOXA5, HOXA2, and HOXA6 genes in CRC were up to 67.62, 58.36, and 31.32%, respectively, and ranked first in CRC among all human tumor tissues. Paired colorectal tumor samples and adjacent non-tumor colorectal tissue samples and four CRC cell lines were selected for MethylTarget™ assays. The results demonstrated that CRC tissues and cells had a stronger methylation status around the 3 HOXA gene promoter regions compared with adjacent non-tumor colonic tissue samples. The Receiver operator characteristic curve (ROC) curves for HOXA genes show excellent diagnostic ability in distinguishing tissue from healthy individuals and CRC patients, especially for Stage I patients (AUC = 0.9979 in HOXA2, 0.9309 in HOXA5, and 0.8025 in HOXA6). An association analysis between the methylation pattern of HOXA genes and clinical indicators was performed and found that HOXA2 methylation was significantly associated with age, N, stage, M, lymphovascular invasion, perineural invasion, lymph node number. HOXA5 methylation was associated with age, T, M, stage, and tumor status, and HOXA6 methylation was associated with age and KRAS mutation. Notably, we found that the highest methylation of HOXA5 and HOXA2 occurs in the early stages of colorectal cancer tissues such as stage I, N0, MO, and non-invasive tissues. The methylation levels declined as tumors progressed. However, methylation level at any stage of the tumor was still significantly higher than in normal tissues (p < 0.0001). The mRNA of the 3 HOXA genes was downregulated in early tumor stages due to hypermethylation of CpG islands adjacent to the promoters of the genes. In addition, hypermethylation of HOXA5 and HOXA6 mainly occurred in patients < 60 years old and with MSI-L, MSS, CIMP.L and non-CIMP tumors. Together, this suggests that epigenetic silencing of 3 adjacent HOXA genes may be an important event in the progression of colorectal cancer.

• HOXA2
• HOXA5
• HOXA6
• biomarker
• colorectal cancer
• early stage
• methylation

• cancer epidemiology
• colorectal cancer
• methylation

• DNA Methylation
• Death-Associated Protein Kinases/genetics
• Female
• Humans
• Lymphoma/genetics
• Lymphoma/mortality
• Lymphoma/pathology
• Lymphoma, Large B-Cell, Diffuse/genetics
• Lymphoma, Large B-Cell, Diffuse/mortality
• Lymphoma, Large B-Cell, Diffuse/pathology
• Male
• Odds Ratio
• Prognosis
• Promoter Regions, Genetic
• Survival Analysis

• Science and Technology Planning Project of Guangdong Province, China
• Natural Science Foundation of Guangdong Province
• Science and Technology Project of Guangzhou Yuexiu District

• Colorectal cancer
• Negative likelihood ratio
• Positive likelihood ratio
• SEPT9 methylation
• Summary receiver operating characteristic

• Adult
• Aged
• Aged, 80 and over
• DNA Methylation/genetics
• Epigenesis, Genetic/genetics
• Female
• Genes, Tumor Suppressor
• Humans
• Male
• Middle Aged
• Multiple Endocrine Neoplasia Type 1/genetics
• Neuroendocrine Tumors/genetics
• Pancreatic Neoplasms/genetics
• Promoter Regions, Genetic/genetics
• Von Hippel-Lindau Tumor Suppressor Protein/genetics

DNA methylation is an essential epigenetic modification involved in regulating the expression of mammalian genomes. A variety of experimental approaches to generate genome-wide or whole-genome DNA methylation data have emerged in recent years. Methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) is one of the major tools used in whole-genome epigenetic studies. However, analyzing this data in terms of accuracy, sensitivity, and speed still remains an important challenge. Existing methods, such as BATMAN and MEDIPS, analyze MeDIP-seq data by dividing the whole genome into equal length windows and assume that each CpG of the same window has the same methylation level. More precise work is necessary to estimate the methylation level of each CpG site in the whole genome. In this paper, we propose a Statistical Inferences with MeDIP-seq Data (SIMD) to infer the methylation level for each CpG site. In addition, we analyze a real dataset for DNA methylation. The results show that our method displays improved precision in detecting differentially methylated CpG sites compared to the existing method. To meet the demands of the application, we have developed an R package called “SIMD”, which is freely available in https://github.com/FocusPaka/SIMD.

• cisatracurium
• colorectal cancer
• invasion
• migration
• p53

• DNA methylation
• Endometrial cancer
• diagnostic marker
• overall survival
• prognostic marker

• Biomarker
• Colorectal cancer
• Epigenetic
• Methylation
• PITX2

• Adenocarcinoma/genetics
• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adenoma/genetics
• Adenoma/mortality
• Adenoma/pathology
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/analysis
• Cell Transformation, Neoplastic/genetics
• Cohort Studies
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• DNA Methylation
• Female
• Homeodomain Proteins/genetics
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Prognosis
• Promoter Regions, Genetic
• Proportional Hazards Models
• Transcription Factors/genetics
• Homeobox Protein PITX2

• Chemograms
• Drug sensitivity
• Individualized medicine
• Molecular signatures
• Pancreatic cancer
• Tumor heterogeneity