An immune-related exosome signature predicts the prognosis and immunotherapy response in ovarian cancer.

BACKGROUND: Cancer-derived exosomes contribute significantly in intracellular communication, particularly during tumorigenesis. Here, we aimed to identify two immune-related ovarian cancer-derived exosomes (IOCEs) subgroups in ovarian cancer (OC) and establish a prognostic model for OC patients based on immune-related IOCEs. METHODS: The Cancer Genome Atlas (TCGA) database was used to obtain RNA-seq data, as well as clinical and prognostic information. Consensus clustering analysis was performed to identify two IOCEs-associated subgroups. Kaplan-Meier analysis was used to compare the overall survival (OS) between IOCEs-high and IOCEs-low subtype. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to investigate the mechanisms and biological effects of differentially expressed genes (DEGs) between the two subtypes. Besides, an IOCE-related prognostic model of OC was constructed by Lasso regression analysis, and the signature was validated using GSE140082 as the validation set. RESULTS: In total, we obtained 21 differentially expressed IOCEs in OC, and identified two IOCE-associated subgroups by consensus clustering. IOCE-low subgroup showed a favorable prognosis while IOCE-high subgroup had a higher level of immune cell infiltration and immune response. GSEA showed that pathways in cancer and immune response were mainly enriched in IOCE-high subgroup. Thus, IOCE-high subgroup may benefit more in immunotherapy treatment. In addition, we constructed a risk model based on nine IOCE-associated genes (CLDN4, AKT2, CSPG5, ALDOC, LTA4H, PSMA2, PSMA5, TCIRG1, ANO6). CONCLUSION: We developed a novel stratification system for OV based on IOCE signature, which could be used to estimate the prognosis as well as immunotherapy for OC patient.

Immune-active tumor-adjacent tissues are associated with favorable prognosis in stage I lung squamous cell carcinoma.

The immunogenomic features of tumor-adjacent lungs (TALs) in stage I lung squamous cell carcinoma (LUSC) are not clear. Multiomics analyses of tumor tissues and paired TALs from 59 stage I LUSC patients were performed. Compared to tumors, TALs exhibited a better-preserved immune contexture indicated by upregulation of immune pathways, increased immune infiltration, and higher expression of immune effector molecules. Notably, TALs had no mutations in PTEN and KEAP1, a lower incidence of human leukocyte antigen (HLA) loss and higher expression of HLA class I genes, major histocompatibility complex (MHC) I chaperones, and interferon (IFN)-γ-associated genes. Digital spatial profiling validated the generally higher immune infiltration in TALs and revealed a higher level of immune heterogeneity in LUSC tumors. Importantly, patients with higher immune infiltration in TALs had significantly longer survival, while high immune heterogeneity was associated with inferior patient survival. Our work can be considered in the selection of patients for adjuvant therapy, especially immunotherapy.

Identifying key genes involved in yellow leaf variation in 'Menghai Huangye' based on biochemical and transcriptomic analysis.

Albino tea plants generally have higher theanine, which causes their tea leaves to taste fresher, and they are an important mutant for the breeding of tea plant varieties. Earlier, we reported an albino germplasm, 'Menghai Huangye' (MHHY), from Yunnan Province and found that it has a lower chlorophyll content during the yellowing stage, but the mechanism underlying low chlorophyll and the yellowing phenotype is still unclear. In this study, the pigment contents of MHHY_May (yellowing, low chlorophyll), MHHY_July (regreening, normal chlorophyll), and YK10_May (green leaves, normal chlorophyll) were determined, and the results showed that the lower chlorophyll content might be an important reason for the formation of the yellowing phenotype of MHHY. Through transcriptome sequencing, we obtained 654 candidates for differentially expressed genes (DEGs), among which 4 genes were related to chlorophyll synthesis, 10 were photosynthesis-related, 34 were HSP family genes, and 19 were transcription factor genes. In addition, we analysed the transcription levels of the key candidate genes in MHHY_May and MHHY_July and found that they are consistent with the expression trends in MHHY_May and YK10_May, which further indicates that the candidate differential genes we identified are likely to be key candidate factors involved in the low chlorophyll content and yellowing of MHHY. In summary, our findings will assist in revealing the low chlorophyll content of MHHY and the formation mechanism of yellowing tea plants and will be applied to the selection and breeding of albino tea cultivars in the future.

Oncogenic Alterations in Histologically Negative Lymph Nodes Are Associated with Prognosis of Patients with Stage I Lung Adenocarcinoma.

Background: Survival of patients with stage I non-small cell lung cancer (NSCLC) varies greatly. We sought to explore whether presence of oncogenic alterations in histologically-negative lymph nodes (LNs) can be of prognostic significance in stage I lung adenocarcinoma (LUAD). Methods: Genomic analysis of oncogenic alterations was applied to 123 stage I LUAD tumors. The same genomic variants identified in primary tumors were examined in corresponding histologically-negative LNs. Results: A total of 102 (82.9%) patients had at least one canonical oncogenic alteration detected in primary tumors, and 57 LNs from 12 patients (11.8%) were found to carry the identical oncogenic alterations detected in the corresponding primary tumor tissues, including EGFR mutations (six cases), KRAS mutations (three cases), ALK fusion (one case), BRAF mutation (one case) and HER2 & NRAS co-mutations (one case). None of these LNs was found to have occult tumor cells by routine pathological assessment or immunohistochemistry staining using antibodies against pan-cytokeratins (AE1/AE3) and the epithelial marker Ber-EP4. The detection rate of oncogenenic alterations in LN was significantly higher in RAS-mutant tumors than EGFR mutant tumors (36.36% verse 7.41%, p = 0.017). Patients with oncogenic alterations in LN showed inferior disease-free survival (DFS, p = 0.025) and overall survival (OS, p = 0.027). Furthermore, patients with RAS-mutations detected in LN had the worst DFS and OS (p = 0.001). Among the 11 patients with RAS mutation in primary tumors, DFS and OS in the four patients with mutations detected in LN were significantly shorter than the remaining seven patients without mutations LN (DFS, p = 0.001, OS, p = 0.002). Conclusions: Genomic analysis has the potential to detect oncogenic alterations in regional LNs for localized LUAD and presence of oncogenic alterations in regional LN may be associated with inferior clinical outcome of stage I LUAD, particularly for certain molecular subgroups. ClinicalTrials.gov ID NCT04266691.

Menghai Huangye, a novel albino tea germplasm with high theanine content and a high catechin index.

Yunnan Province has a very wide diversity of tea germplasm resources. A variety of special tea germplasms with outstanding traits have been discovered, including tea germplasms with high anthocyanin content and low caffeine content. Albino tea cultivars generally have higher contents of theanine that contribute to the umami taste, and the quality of tea brewed from it is higher. The catechin index (CI), the ratio of dihydroxylated catechins (DIC) to trihydroxylated catechins (TRIC), is a crucial index of suitability for processing tea. In this study, the albino tea plant Menghai Huangye (MHHY) with yellow leaves was identified. Analysis of the biochemical components revealed that MHHY was enriched in theanine and the total catechins (TC) were lower than Yunkang 10 (YK10). In addition, the CI value of MHHY was extremely significantly higher than that of YK10. Metabolic profile of catechins and the related gene expression profile analysis found that the coordinated expression of the key branch genes F3'H and F3'5'Ha for the synthesis of DIC and TRIC in tea plant was closely related to the high CI and low TC of MHHY. Further analysis of the F3'H promoter showed that a 284-bp deletion mutation was present in the F3'H promoter of MHHY, containing the binding sites of the transcriptional repressor MYB4 involved in flavonoid metabolism, which might be an important reason for the up-regulated expression of F3'H in MHHY. Overall, this study provides a theoretical basis for understanding the characteristics of albino tea germplasm resources and efficiently utilizing high-CI tea germplasm resources.

The association of CMTM6 expression with prognosis and PD-L1 expression in triple-negative breast cancer.

BACKGROUND: Immune checkpoint inhibitors play a vital role in triple-negative breast cancer (TNBC) immunotherapy. A recent study showed that chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) has a crucial role in programmed death-ligand 1 (PD-L1) stability. The aim of this study was to investigate the relationship between CMTM6 and PD-L1 in TNBC and the association with clinical characteristics. METHODS: A total of 143 patients, including 75 with human epidermal growth factor receptor 2 (HER2)-driven breast cancer and 68 with TNBC, were included in this study. In 83 paired primary breast cancers (PBCs) and metastatic breast cancers (MBC) comprising 45 HER2-driven breast cancers and 38 TNBC, CMTM6 and PD-L1 were detected based on immunohistochemistry (IHC) with FFPE tissues. Another 60 PBCs comprising 30 HER2-driven breast cancers and 30 TNBC in order to detect CMTM6 and PD-L1 mRNA expressions based on real-time polymerase chain reaction (RT-PCR) using frozen tissues. Furthermore, 153 patients comprising 30 TNBC and 123 HER2-driven breast cancer based on The Cancer Genome Atlas (TCGA) database were used to confirm the difference mRNA expression. RESULTS: The expression of CMTM6 in patients with TNBC was significantly higher than in those with HER2-driven PBC (IHC, P=0.036, mRNA, P=0.036, TCGA dataset, P=0.039). CMTM6 was correlated with PD-L1 based on IHC in triple-negative MBC (P=0.004); the same result was found based on mRNA data in triple- negative PBC (P=0.021). Moreover, a high expression of CMTM6 in TNBC was associated with poor progression-free survival (PFS) (P=0.030, 95% CI: 1.08-4.57, HR =2.22). After multiple Cox regression analysis, CMTM6 in TNBC emerged as an independent risk factor for PFS (P=0.027, 95% CI: 1.11-5.20, HR =2.40). The expression of PD-L1 was negatively correlated with lymph node metastasis (P=0.026) and was not associated with PFS. CONCLUSIONS: The expression of CMTM6 was higher in TNBC than in HER2-driven breast cancer. In TNBC, CMTM6 was correlated with PD-L1 expression, and potentially could be used as an independent risk factor for predicting PFS.

Comparative transcriptomic analysis of the tea plant (Camellia sinensis) reveals key genes involved in pistil deletion.

BACKGROUND: The growth process of the tea plant (Camellia sinensis) includes vegetative growth and reproductive growth. The reproductive growth period is relatively long (approximately 1.5 years), during which a large number of nutrients are consumed, resulting in reduced tea yield and quality, accelerated aging, and shortened economic life of the tea plant. The formation of unisexual and sterile flowers can weaken the reproductive growth process of the tea plant. To further clarify the molecular mechanisms of pistil deletion in the tea plant, we investigated the transcriptome profiles in the pistil-deficient tea plant (CRQS), wild tea plant (WT), and cultivated tea plant (CT) by using RNA-Seq. RESULTS: A total of 3683 differentially expressed genes were observed between CRQS and WT flower buds, with 2064 upregulated and 1619 downregulated in the CRQS flower buds. These genes were mainly involved in the regulation of molecular function and biological processes. Ethylene synthesis-related ACC synthase genes were significantly upregulated and ACC oxidase genes were significantly downregulated. Further analysis revealed that one of the WIP transcription factors involved in ethylene synthesis was significantly upregulated. Moreover, AP1 and STK, genes related to flower development, were significantly upregulated and downregulated, respectively. CONCLUSIONS: The transcriptome analysis indicated that the formation of flower buds with pistil deletion is a complex biological process. Our study identified ethylene synthesis, transcription factor WIP, and A and D-class genes, which warrant further investigation to understand the cause of pistil deletion in flower bud formation.

Genome-wide analysis reveals the association between alternative splicing and DNA methylation across human solid tumors.

BACKGROUND: Dysregulation of alternative splicing (AS) is a critical signature of cancer. However, the regulatory mechanisms of cancer-specific AS events, especially the impact of DNA methylation, are poorly understood. METHODS: By using The Cancer Genome Atlas (TCGA) SpliceSeq and TCGA data for ten solid tumor types, association analysis was performed to characterize the potential link between cancer-specific AS and DNA methylation. Functional and pathway enrichment analyses were performed, and the protein-protein interaction (PPI) network was constructed with the String website. The prognostic analysis was carried out with multivariate Cox regressions models. RESULTS: 15,818 AS events in 3955 annotated genes were identified across ten solid tumor types. The different DNA methylation patterns between tumor and normal tissues at the corresponding alternative spliced exon boundaries were shown, and 51.3% of CpG sites (CpGs) revealed hypomethylated in tumors. Notably, 607 CpGs were found to be highly correlated with 369 cancer-specific AS events after permutation tests. Among them, the hypomethylated CpGs account for 52.7%, and the number of down-regulated exons was 173. Furthermore, we found 38 AS events in 35 genes could serve as new molecular biomarkers to predict patient survival. CONCLUSIONS: Our study described the relationship between DNA methylation and AS events across ten human solid tumor types and provided new insights into intragenic DNA methylation and exon usage during the AS process.

Use of multiple regression models for predicting the formation of bromoform and dibromochloromethane during ballast water treatment based on an advanced oxidation process.

Disinfection byproducts (DBPs) generated by ballast water treatment have become a concern worldwide because of their potential threat to the marine environment. Predicting the relative DBP concentrations after disinfection could enable better control of DBP formation. However, there is no appropriate method of evaluating DBP formation in a full-scale ballast water treatment system (BWTS). In this study, multiple regression models were developed for predicting the dibromochloromethane (DBCM) and bromoform (TBM) concentrations produced by an emergency BWTS using field experimental data from ballast water treatments conducted at Dalian Port, China. Six combinations of independent variables [including several water parameters and/or the total residual oxidant (TRO) concentration] were evaluated to construct mathematical prediction formulas based on a polynomial linear model and logarithmic regression model. Further, statistical analyses were performed to verify and determine the appropriate mathematical models for DBCM and TBM formation, which were ultimately validated using additional field experimental data. The polynomial linear model with four variables (temperature, salinity, chlorophyll, and TRO) and the logarithmic regression model with seven variables (temperature, salinity, dissolved oxygen, pH, turbidity, chlorophyll, and TRO) exhibited good reproducibility and could be used to predict the DBCM and TBM concentrations, respectively. The validation results indicated that the developed models could accurately predict DBP concentrations, with no significant statistical difference from the measured values. The results of this work could provide a theoretical basis and data reference for ballast water treatment control in engineering applications of emergency BWTSs.

A novel discriminating colorectal cancer model for differentiating normal and tumor tissues.

AIM: To construct a model discriminating colorectal cancer (CRC) based on differential DNA methylation. MATERIALS & METHODS: The CRC-related methylation-modulated genes were retrieved from literature. The methylation levels of CpG sites in the promoter regions and the first exons of candidate genes were verified in The Cancer Genome Atlas data. A model for discriminating CRC based on methylation levels was established using least absolute shrinkage and selection operator regression. RESULTS: Five new differentially methylated CpG sites were identified and further validated in 94 Chinese CRC patients. A five-CpG-based panel was constructed, with the area under the curve values of 0.999 in The Cancer Genome Atlas data and 0.943 in Chinese patients, respectively. CONCLUSION: This five-CpG-based panel is a practical and reliable tool for CRC discrimination.

Application of a hydroxyl-radical-based disinfection system for ballast water.

A hydroxyl radical (OH) ballast water treatment system (BWTS) was developed and applied to inactivate entrained organisms in a 10,000-ton oceanic ship, where OH was produced by a strong ionization discharge combined with a water jet cavitation effect. The calculated OH generation rate was 1373.4 µM min-1 in ballast water, which is much higher than that in other advanced oxidative processes such as photocatalysis. As a result, non-indigenous red tide algae were inactivated to meet the ballast water discharge standards (<10 cells mL-1) of the International Maritime Organization. The ratio of variable fluorescence to maximum fluorescence (Fv/Fm) for algal chlorophyll rapidly decreased to zero within a contact time of only 6 s, indicating complete inactivation of algae. Observation under a scanning electron microscope showed no cellular materials were released by algal cells upon OH inactivation. A risk assessment of the OH treatment system was conducted, and the ratios of predicted environmental concentrations to predicted no effect concentrations of all detected disinfection byproducts were less than 1, even at a worst-case oxidant concentration of 2.41 mg L-1. Ship ballast water treated using OH inactivation is safe for marine environments. Finally, the energy consumption and operational costs of the OH BWTS were found to be 0.033 kWh m-3 and CNY 0.03 m-3, respectively.

Solid-phase microextraction of volatile organic compounds in headspace of PM-induced MRC-5 cell lines.

The exploration of volatile organic compounds (VOCs) produced by cell lines may be a powerful and non-invasive tool for the study of the health risk of human exposure to atmospheric particulate matter (PM). In this work, we developed a sensitive solid phase microextraction-gas chromatography-mass spectrometry method (SPME-GC-MS) to analyze VOCs in breathed gas of PM2.5-induced human embryonic fibroblast cell line (MRC-5). A novel graphene oxide/polyaniline/polydopamine (GO/PANI/PDA) coating was prepared on a stainless steel wire via electrochemical deposition and self-polymerization for the first time. The GO/PANI/PDA coating exhibited high extraction efficiency, good thermal stability (> 380 ℃), excellent mechanical stability as well as long service time (> 150 times). Parameters that may affect the results were optimized systematically. Under the optimal conditions, VOCs including benzene series, aldehydes and alkane were detected with low limit of detection (0.2-2.0 µg L-1) and good correlation (correlation coefficients above 0.9922). The relative standard deviations of within-day and between-day were 1.1-8.4% and 0.2-11.2%, respectively. Satisfactory recoveries of 82-117% indicated good repeatability of the method. The method has been successfully applied for the determination of target VOCs in the headspace gas of PM2.5-induced MRC-5 cell. And it is expected to provide an alternative tool for the study of cytotoxicology of atmospheric particulates.

Integrated analyses of multi-omics reveal global patterns of methylation and hydroxymethylation and screen the tumor suppressive roles of HADHB in colorectal cancer.

Background: DNA methylation is an important epigenetic modification, associated with gene expression. 5-Methylcytosine and 5-hydroxymethylcytosine are two epigenetic hallmarks that maintain the equilibrium of epigenetic reprogramming. Disequilibrium in genomic methylation leads to carcinogenesis. The purpose of this study was to elucidate the epigenetic mechanisms of DNA methylation and hydroxymethylation in the carcinogenesis of colorectal cancer. Methods: Genome-wide patterns of DNA methylation and hydroxymethylation in six paired colorectal tumor tissues and corresponding normal tissues were determined using immunoprecipitation and sequencing. Transcriptional expression was determined by RNA sequencing (RNA-Seq). Groupwise differential methylation regions (DMR), differential hydroxymethylation regions (DhMR), and differentially expressed gene (DEG) regions were identified. Epigenetic biomarkers were screened by integrating DMR, DhMR, and DEGs and confirmed using functional analysis. Results: We identified a genome-wide distinct hydroxymethylation pattern that could be used as an epigenetic biomarker for clearly differentiating colorectal tumor tissues from normal tissues. We identified 59,249 DMRs, 187,172 DhMRs, and 948 DEGs by comparing between tumors and normal tissues. After cross-matching genes containing DMRs or DhMRs with DEGs, we screened seven genes that were aberrantly regulated by DNA methylation in tumors. Furthermore, hypermethylation of the HADHB gene was persistently found to be correlated with downregulation of its transcription in colorectal cancer (CRC). These findings were confirmed in other patients of colorectal cancer. Tumor functional analysis indicated that HADHB reduced cancer cell migration and invasiveness. These findings suggested its possible role as a tumor suppressor gene (TSG). Conclusion: This study reveals the global patterns of methylation and hydroxymethylation in CRC. Several CRC-associated genes were screened with multi-omic analysis. Aberrant methylation and hydroxymethylation were found to be in the carcinogenesis of CRC.

DNA hydroxymethylation of colorectal primary carcinoma and its association with survival.

METHODS: A total of 71 cases of colorectal carcinoma with hepatic metastasis were enrolled from the Department of Pathology of SIR RUN RUN SHAW Hospital. Paired primary tumors, hepatic metastases, and normal mucosa samples were collected from formalin-fixed paraffin-embedded tissues by manual macrodissection. And global levels of DNA methylation and hydroxymethylation in these tissues, measured by an ELISA-like microplate-based colorimetric methods. The immunohistochemical expression of 5-methylcytosine and 5-hydroxymethylcytosine were analyzed also. RESULTS: The levels of DNA methylation in both primary and metastatic tumors were elevated when compared with normal mucosa, while DNA hydroxymethylation decreased slightly in those tissues. Similar results were observed in immunohistochemical staining. DNA methylation in hepatic metastases differed significantly in lymph node metastases (P = 0.037). And DNA hydroxymethylation in colorectal primary carcinoma was significantly different between tumor grade group (P = 0.018) and gender group (P = 0.048) respectively. And survival analyzes revealed that higher levels DNA hydroxymethylation were associated with better prognosis in colorectal primary carcinoma (P < 0.05). CONCLUSION: DNA hydroxymethylation correlated with less aggressive tumor behavior in colorectal cancer and were identified as an independent prognostic factor in patients' overall survival, and downregulation of DNA hydroxymethylation may serve as a useful biomarker for colorectal cancer prognosis evaluation.

The estimation for ballast water discharged to China from 2007 to 2014.

Ballast water has been identified as one of the main causes for worldwide transfer of non-indigenous marine species. The volume and source of ballast water are the fundamental elements for an evaluation of the risk posed. However, it is difficult to obtain the volume of ballast water discharged to China, because of the absence of information platform, and until now there is no public report. In this paper, the total volume of ballast water discharged to China and Chinese five major port-groups were estimated. Results showed: the total volume of ballast water exhibited a trend of slow increase from 2007 to 2014, and reached 311 million tons in 2014. Yangtze River Delta received the highest volume of ballast water among all port-groups. The information provided in this research may play an important role in helping policy decision-makers manage such coastal discharges.

Association of TET1 expression with colorectal cancer progression.

OBJECTIVE: The ten-eleven translocation (TET) proteins, as methylcytosine dioxygenases, catalyze 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). The altered expression of TET1 disrupts the balance between DNA methylation and demethylation. This alteration has been reported to be associated with carcinogenesis in various malignancies. The aim of the present study was to investigate changes in expression and the role of TET1 in colorectal cancer (CRC). MATERIAL AND METHODS: A total of 109 CRC patients who underwent radical surgical colon resection were enrolled. The QuantiGene Plex Assay was used to detect the expression of TET1 in CRC tissues and matching adjacent normal tissues. We analyzed the associations between TET1 expression levels and various clinicopathologic features of CRC. TET1 overexpression and depletion cells were constructed to investigate its biological role in CRC. RESULTS: Compared to normal tissues, the expression level of TET1 in CRC was significantly lower. The ratio of TET1 in CRC tissues to that in adjacent normal tissues (C/N-TET1) was an independent overall survival predictive factor. Moreover, in vitro studies showed that TET1 could inhibit cell growth and promote cell metastasis and invasion. CONCLUSIONS: These findings indicated that TET1 played a multifaceted role in the pathogenesis of CRC, and thereby resulting in multiple effects on tumor progression.

Higher Levels of Magnesium and Lower Levels of Calcium in Whole Blood Are Positively Correlated with the Metabolic Syndrome in a Chinese Population: A Case-Control Study.

Magnesium (Mg) and calcium (Ca) are essential for numerous kinds of metabolisms in human body. To investigate the associations between Mg and Ca and the ratio of Ca to Mg (Ca/Mg) in whole blood with metabolic syndrome (MetS) in a Chinese population, a matched case-control study including 204 MetS patients and 204 healthy controls (aged 48-89) was carried out in 2011. MetS were diagnosed according to the criteria of Chinese Diabetes Society. Controls had no abnormal metabolic components and were matched with cases by age, gender and region. Blood samples were collected in the morning after an overnight fast. Whole blood Mg and Ca were determined by flame atomic absorption spectrometry. Subjects who were male constituted 44.1% of the part of this study. The average age was 64.0 ± 7.18, and the average body mass index was 24.3 ± 3.75. The MetS group showed significantly higher Mg and lower Ca and Ca/Mg as compared with the control group. Comparing with the bottom tertile (T1) of Mg, increased ORs for MetS were found in median tertile (T2) and top tertile (T3) of Mg. For Ca, T2 and T3 were negatively associated with MetS. Inverse relationship was also found between Ca/Mg ratio and MetS. Our findings suggested that increased Mg and decreased Ca and Ca/Mg in whole blood were correlated with MetS in Chinese adults.

Multiple Functions of Ten-eleven Translocation 1 during Tumorigenesis.

OBJECTIVE: Aberrant expression of ten-eleven translocation 1 (TET1) plays a critical role in tumor development and progression. We systematically summarized the latest research progress on the role and mechanisms of TET1 in cancer biology. DATA SOURCES: Relevant articles published in English from 1980 to April 2016 were selected from the PubMed database. The terms "ten-eleven translocation 1," "5mC," "5hmC," "microRNA," "hypoxia," and "embryonic stem cell" were used for the search. STUDY SELECTION: Articles focusing on the role and mechanism of TET1 in tumor were reviewed, including clinical and basic research articles. RESULTS: TET proteins, the key enzymes converting 5-methylcytosine to 5-hydroxymethylcytosine, play vital roles in DNA demethylation regulation. Recent studies have shown that loss of TET1 is associated with tumorigenesis and can be used as a potential biomarker for cancer therapy, which indicates that TET1 serves as tumor suppressor gene. Moreover, besides its dioxygenase activity, TET1 could induce epithelial-mesenchymal transition and act as a coactivator to regulate gene transcription, such as developmental regulator in embryonic stem cells (ESCs) and hypoxia-responsive gene in cancer. The regulation of TET1 is also correlated with microRNA in a posttranscriptional modification process. Hence, it is complex but critical to comprehend the mechanisms of TET1 in the biology of ESCs and cancer. CONCLUSIONS: TET1 not only serves as a demethylation enzyme but also plays multiple roles during tumorigenesis and progression. More studies should be carried out to elucidate the exact mechanisms of TET1 and its associations with cancer before considering it as a therapeutic tool.