Methylation-regulated tumor suppressor gene PDE7B promotes HCC invasion and metastasis through the PI3K/AKT signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high mortality rate, and the mechanisms underlying tumor development and progression remain unclear. However, inactivated tumor suppressor genes might play key roles. DNA methylation is a critical regulatory mechanism for inactivating tumor suppressor genes in HCC. Therefore, this study investigated methylation-related tumor suppressors in HCC to identify potential biomarkers and therapeutic targets. METHODS: We assessed genome-wide DNA methylation in HCC using whole genome bisulfite sequencing (WGBS) and RNA sequencing, respectively, and identified the differential expression of methylation-related genes, and finally screened phosphodiesterase 7B (PDE7B) for the study. The correlation between PDE7B expression and clinical features was then assessed. We then analyzed the changes of PDE7B expression in HCC cells before and after DNA methyltransferase inhibitor treatment by MassArray nucleic acid mass spectrometry. Furthermore, HCC cell lines overexpressing PDE7B were constructed to investigate its effect on HCC cell function. Finally, GO and KEGG were applied for the enrichment analysis of PDE7B-related pathways, and their effects on the expression of pathway proteins and EMT-related factors in HCC cells were preliminarily explored. RESULTS: HCC exhibited a genome-wide hypomethylation pattern. We screened 713 hypomethylated and 362 hypermethylated mCG regions in HCC and adjacent normal tissues. GO analysis showed that the main molecular functions of hypermethylation and hypomethylation were "DNA-binding transcriptional activator activity" and "structural component of ribosomes", respectively, whereas KEGG analysis showed that they were enriched in "bile secretion" and "Ras-associated protein-1 (Rap1) signaling pathway", respectively. PDE7B expression was significantly down-regulated in HCC tissues, and this low expression was negatively correlated with recurrence and prognosis of HCC. In addition, DNA methylation regulates PDE7B expression in HCC. On the contrary, overexpression of PDE7B inhibited tumor proliferation and metastasis in vitro. In addition, PDE7B-related genes were mainly enriched in the PI3K/ATK signaling pathway, and PDE7B overexpression inhibited the progression of PI3K/ATK signaling pathway-related proteins and EMT. CONCLUSION: PDE7B expression in HCC may be regulated by promoter methylation. PDE7B can regulate the EMT process in HCC cells through the PI3K/AKT pathway, which in turn affects HCC metastasis and invasion.

Causal associations of antioxidants with Alzheimer's disease and cognitive function: a Mendelian randomisation study.

BACKGROUND: Circulating antioxidants are associated with a lower risk of Alzheimer's disease (AD) in observational studies, suggesting potential target areas for intervention. However, whether the associations are causal remains unclear. Here, we studied the causality between antioxidants and AD or cognitive function using two-sample Mendelian randomisation (MR). METHODS: Single nucleotide polymorphisms strongly (p<5×10-8) associated with antioxidants (vitamin A, vitamin C, zinc, selenium, ß-carotene and urate) and outcomes (AD, cognitive performance and reaction time) were obtained from the largest and most recent genome-wide association studies (GWAS). MR inverse variance weighting (IVW) and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used for data analysis. RESULTS: Higher genetically determined selenium level was associated with 5% higher risk of AD (OR 1.047, 95% CI 1.005 to 1.091, p=0.028) using IVW. Higher genetically determined urate level was associated with worse cognitive performance (ß=-0.026, 95% CI -0.044 to -0.008, p=0.005) using MR-PRESSO. No association between the other antioxidants and AD, cognitive performance and reaction time was found. Similar results were found in the sensitivity analyses. CONCLUSION: Our results suggest that lifelong exposure to higher selenium may be associated with a higher risk of AD, and higher urate levels could be associated with worse cognitive performance. Further analyses using larger GWAS of antioxidants are warranted to confirm these observations. Our results suggest that caution is needed in the interpretation of traditional observational evidence on the neuroprotective effects of antioxidants.

Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma.

BACKGROUND: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

Prevalence and influencing factors of hyperuricemia in middle-aged and older adults in the Yao minority area of China: a cross-sectional study.

Hyperuricemia (HUA) endangers human health, and its prevalence has increased rapidly in recent decades. The current study investigated HUA's prevalence and influencing factors in Gongcheng, southern China. A cross-sectional investigation was conducted; 2128 participants aged 30-93 years were included from 2018 to 2019. Univariate and multivariate logistic regression models were used to screen HUA variables. A Bayesian network model was constructed using the PC algorithm to evaluate the association between influencing factors and HUA. The prevalence of HUA was 15.6% (23.2% in men, 10.7% in women). After screening the variables using a logistic regression analysis model, fatty liver disease (FLD), dyslipidemia, abdominal obesity, creatinine (CREA), somatotype, bone mass, drinking, and physical activity level at work were included in the Bayesian network model. The model results showed that dyslipidemia, somatotype, CREA, and drinking were directly related to HUA. Bone mass and FLD were indirectly associated with HUA by affecting the somatotype. The prevalence of HUA in Gongcheng was high in China. The prevalence of HUA was related to somatotype, drinking, bone mass, physical activity level at work, and other metabolic diseases. A good diet and moderate exercise are recommended to maintain a healthy somatotype and reduce the prevalence rate of HUA.

Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma.

BACKGROUND: Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC). METHODS: The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307. RESULTS: Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn't show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4+ T cells had a better overall survival than those with low infiltration of CD4+ T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4+ and CD8+ T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy. CONCLUSIONS: CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment.

Adherence to dietary guide for elderly adults and health risks of older adults in ethnic minority areas in China: a cross-sectional study.

BACKGROUND: The impact of dietary guidelines on health in ethnic minority regions needs to be further explored because of multiple sociocultural factors. Therefore, this study was conducted to analyze the association between adherence to dietary guidelines and health risks in an elderly population in an ethnic minority region. METHODS: A cross-sectional survey was conducted among 836 older adults in ethnic minority areas. They were asked to describe their daily dietary intake levels through a semi-quantitative food frequency questionnaire. The closeness coefficient for each study subject was calculated by using the technique for order preference by similarity to an ideal solution (TOPSIS), which measures the adherence to Dietary Guide for Elderly Adults (DGEA). Regression models were used to analyze the association between adherence and health risks. RESULTS: The daily food of the elderly in this area comprised cereals and vegetables. They had low intake of milk, dairy products, and water and high intake of salt. The closeness coefficient for the total population was 0.51, and the adherence of this population to dietary guidelines for the elderly was low. In both the crude model and the models adjusted for covariates, the closeness coefficient was not significantly associated with clinical indicators and health outcomes (p > 0.05). CONCLUSIONS: No association was found between adherence to large sample-based dietary guidelines and clinical indicators or health outcomes in ethnic minority populations. The applicability of dietary guidelines to ethnic minority areas and whether they yield the expected health benefits require further study.

Expression and clinical significance of CMTM1 in hepatocellular carcinoma.

BACKGROUND: CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. METHODS: The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan-Meier model. RESULTS: Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). CONCLUSION: CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

Clinical Significance of POM121 Expression in Lung Cancer.

Aims: The aim of this study was to examine the RNA and protein expression levels and clinical significance of the pore membrane protein 121 kDa (POM121) in lung cancer. Materials and Methods: Paired lung cancer and adjacent nontumor tissues were obtained from lung cancer patients to measure the expression of POM121 by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Patient clinical and pathological data were collected to analyze their relationships with POM121 protein expression levels by chi-square test and log-rank test, respectively. Results: POM121 mRNA and protein expression were both upregulated in lung cancer tissues. POM121 protein expression was observed in 48.00% (36/75) of lung cancer tissues and 25.33% (19/75) of adjacent nontumor tissues. A chi-square analysis indicated that this difference was statistically significant (p < 0.05). Furthermore, we found that POM121 protein expression was correlated with gender, tumor node metastasis stage, and lymphatic metastasis (p < 0.05). In addition, we found a significant relationship among POM121 expression, gender, and metastasis based on a multivariate logistic regression analysis. A Kaplan-Meier survival analysis indicated that lung cancer patients with POM121 expression had a poorer prognosis than those without POM121 expression (p < 0.05). Conclusion: POM121 protein expression is associated with lung cancer metastasis and is a potential prognostic biomarker for lung cancer patients.

M6A Demethylase FTO Plays a Tumor Suppressor Role in Thyroid Cancer.

The purpose of this study was to investigate the expression and clinical significance of N6-methyladenosine demethylase FTO in thyroid cancer. Bioinformatic analysis showed that FTO expression was downregulated in thyroid cancer tissues and correlated with lymph node metastasis in thyroid cancer patients. We conducted experimental verification by collecting Asian samples. The results of quantitative reverse transcription-PCR showed that the mRNA expression of FTO in the blood of 30 thyroid cancer patients was lower than that of the control population. At the same time, we found that FTO expression was negative in tissues of 16/56 (28.57%) thyroid cancer cases and 4/40 (10.00%) nontumor thyroid cases through the immunohistochemical method, indicating a lower FTO expression in thyroid cancer tissues than nontumor thyroid tissues (p < 0.05). In addition, the protein expression of FTO was significantly related to the tumor grade and lymph node metastasis in thyroid cancer patients (p < 0.05), but not to other clinicopathological features. Multivariate logistic regression analysis showed that FTO expression was an independent risk factor for tumor grade. Survival analysis showed no significant difference in the disease-free survival time of thyroid cancer patients between high expression and low expression groups of FTO. Furthermore, bioinformatic analysis found that promoter DNA methylation and copy number variation might cause downregulated FTO and then affect TP53 pathways in thyroid cancer. We found that FTO expression was downregulated in thyroid cancer tissues and related to the progression of thyroid cancer, suggesting a tumor suppressor role of FTO in thyroid cancer.

Retraction Note to: Correlations between chromobox homolog 8 and key factors of epithelial-mesenchymal transition in hepatocellular carcinoma.

[This retracts the article DOI: 10.1186/s12935-019-1063-z.].

Down-Regulated CMTM2 Promotes Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.

BACKGROUND: Our recent study identified that human chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 2 (CMTM2) was deregulated in hepatocellular carcinoma (HCC) tissues and posed as a potential tumor suppressor. However, the mechanism of CMTM2 in HCC occurrence and development has not been well elaborated. MATERIALS AND METHODS: The expression of CMTM2 was knocked-down by RNA interruption in Huh-7 and SMMC7721 cells. Cell proliferation ability was detected by CCK8 test and colony formation assay. The cell invasion and migration were measured by wound healing and Transwell assay. RESULTS: We found that the cell proliferation was significantly increased by interruption of CMTM2 expression, both in Huh-7 and SMMC7721 cells. Moreover, down-regulated CMTM2 could promote the invasion and migration ability of HCC cells through inducing the epithelial-mesenchymal transition (EMT) process. We further discovered that both the expression of CMTM2 and the EMT-associated marker E-cadherin were decreased in the same thirty cases of HCC tissues compared with the corresponding adjacent non-tumor tissues. Pearson correlation test showed that there was a significantly positive correlation between CMTM2 and E-cadherin in HCC tissues (P<0.05). CONCLUSION: Based on the results of cell model and HCC tissues, our study suggests that down-regulated CMTM2 promotes HCC metastasis through inducing the EMT process.

Blood donor recruitment in Guangzhou, China, during the 2019 novel coronavirus (COVID-19) epidemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic affected blood collection in Guangzhou, China. STUDY DESIGN AND METHODS: This paper includes three studies. The observational study reported the trends of blood collection during the epidemic in Guangzhou, China. The cross-sectional survey investigated factors influencing blood donation during the COVID-19 epidemic, and a self-administered questionnaire was given to 1584 street whole blood donors (SWBDs) who donated during the epidemic. The randomized controlled trial involved 19 491 SWBDs who donated in 2019 but did not donate during the epidemic. Trial participants were randomly assigned to two intervention groups: Group 1 completed Questionnaire 1, which contained precautionary measures in response to COVID-19 and other messages about blood donation during the epidemic; Group 2 completed Questionnaire 2, which did not include this information. A control group did not receive any questionnaire. RESULTS: As measures were implemented, the number of blood donors increased accordingly. Both first-time and repeat SWBDs perceived the same level of blood need and donated blood because it would save lives. SWBDs who completed Questionnaire 1 expressed a greater intention to donate during the epidemic. Enabling blood donors to perceive a higher level of blood need and a lower level of COVID-19 infection risk related to blood donation mobilized experienced SWBDs to donate within 3 weeks. Intention-to-treat analyses and average-treatment-effect-on-the-treated estimations confirmed that Questionnaire 1 could motivate SWBDs to actually donate blood. CONCLUSION: Various measures could ease blood shortage during the COVID-19 epidemic. Administration of Questionnaire 1 could increase blood donations during the epidemic.

An analysis of spatiotemporal pattern for COIVD-19 in China based on space-time cube.

This study seeks to examine and analyze the spatial and temporal patterns of 2019 novel coronavirus disease (COVID-19) outbreaks and identify the spatiotemporal distribution characteristics and changing trends of cases. Hence, local outlier analysis and emerging spatiotemporal hot spot analysis were performed to analyze the spatiotemporal clustering pattern and cold/hot spot trends of COVID-19 cases based on space-time cube during the period from 23 January 2020 to 24 February 2020. The main findings are as follows: (1) The outbreak had spread rapidly throughout the country within a short time and the current totality incidence rate has decreased. (2) The spatiotemporal distribution of cases was uneven. In terms of the spatiotemporal clustering pattern, Wuhan and Shiyan city were the center as both cities had high-high clustering pattern with a surrounding unstable multiple-type pattern in partial areas of Henan, Anhui, Jiangxi, and Hunan provinces, and Chongqing city. Those regions are continuously in the hot spot on the spatiotemporal tendency. (3) The spatiotemporal analysis technology based on the space-time cube can analyze comprehensively the spatiotemporal pattern of epidemiological data and produce a visual output of the consequences, which can reflect intuitively the distribution and trend of data in space-time. Therefore, the Chinese government should strengthen the prevention and control efforts in a targeted manner to cope with a highly changeable situation.

Effective methods for reactivating inactive blood donors: a stratified randomised controlled study.

BACKGROUND: Recruiting of sufficient numbers of donors of blood products is vital worldwide. In this study we assessed the efficacy and cost-effectiveness of telephone calls and SMS reminders for re-recruitment of inactive blood donors. METHODS: This single-centre, non-blinded, parallel randomised controlled trial in Guangzhou, China included 11,880 inactive blood donors whose last donation was between January 1 and June 30, 2014. The donors were randomly assigned to one of two intervention groups (telephone call or short message service [SMS] communications) or to a control group without intervention. SMS messages with altruistic appeal were adopted in the SMS group; in addition to altruistic appeal, reasons for deferral of blood donation were also asked in the telephone group. All participants were followed up for 1 year. The primary outcome was re-donation rate, and rates in different groups were compared by intention-to-treat (ITT) analysis and estimation of the average treatment effect on the treated (ATT). Secondary outcomes were the self-reported deterrents. Other outcomes included the re-donation interval, and the incremental cost-effectiveness ratio (ICER) of telephone calls and SMS reminders on re-recruitment. RESULTS: ITT analysis revealed no significant differences in the re-donation rate among the three groups. ATT estimations indicated that among compliers, telephone calls significantly increased re-donation compared to both SMS reminders and no intervention. Donor return behaviour was positively associated with receiving reminders successfully, being male, older age, and previous donation history. The SMS reminder prompted donors to return sooner than no reminder within 6 months, and according to ICER calculations, SMS reminders were more cost-effective than telephone calls. Donors reported time constraints as the most main causes of self-deferral in the telephone group, and altruistic appeal had a positive effect on these donors. CONCLUSIONS: Interventions to reactivate inactive blood donors can be effective, with telephone calls prompting more donors to return but at a greater cost than SMS messages. SMS reminder with altruistic appeal can urge donors to re-donate sooner within 6 months than no reminder. TRIAL REGISTRATION: NCT03366441 (Reactivation of Inactive Blood Donors). Retrospectively registered 4 December 2017.

Downregulated CMTM2 Poses Potential Clinical Significance in Hepatocellular Carcinoma.

This study aimed to investigate the expression and clinical significance of chemokine-like factor-like MARVEL transmembrane domain-containing family member 2 (CMTM2) in hepatocellular carcinoma (HCC) tissues. Bioinformatics analysis showed that CMTM2 was downregulated in HCC tissues and correlated with vascular invasion of HCC patients. The immunohistochemistry (IHC) method found that CMTM2 expression was negative in 29/75 (38.67%) cases of HCC tissues and 13/75 (17.33%) cases of paracancerous tissues, also showed a significantly lower expression of CMTM2 in HCC tissues than the paired paracancerous tissues (p < 0.05). Moreover, CMTM2 expression was significantly correlated with tumor grade of HCC patients (p < 0.05), but had no relationship with other clinicopathological features. In addition, multivariate logistic regression analysis indicated that tumor grade was an independent risk factor for CMTM2 expression. The survival time of HCC patients between high and low expression of CMTM2 had no difference by bioinformatics analysis, but the IHC result showed that the negative expression of CMTM2 was related to a poor prognosis of HCC patients. Further COX regression analysis showed that CMTM2 expression was an independent protective factor for the prognosis of HCC patients. We identify that CMTM2 is downregulated in HCC tissues and correlated with the prognosis of HCC patients, suggesting a potential tumor suppressor role of CMTM2 in HCC progression.

Okadaic acid promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting protein phosphatase 2A.

As a specific inhibitor of serine/threonine protein phosphatases, okadaic acid (OA) has been found to be a tumor promoter. However, whether OA plays a role in metastasis of hepatocellular carcinoma (HCC) has not been well elucidated. In this study, Hep3B and HepG2 cells were treated with different doses of OA and the cell viability was determined by CCK8 test. As a result, Hep3B and HepG2 cells showed no obvious cytotoxicity after OA treatment below 20 or 25 nM for 12 or 24 hours. However, wound healing, invasion, and migration abilities of HCC cells were significantly enhanced in the OA-treated groups than those of the control group (P < .05), measured by cell scratching and BD transwell assays. Moreover, we found that the expression of epithelial-mesenchymal transition (EMT)-related key factors was changed upon OA treatment in a dose-dependent manner. In addition, the activity of protein phosphatase 2A (PP2A) in OA-treated cells was also decreased significantly compared with the control cells (P < .05). Interfering of PP2A subunit A or C caused a similar expression change of EMT-related key factors as the OA treatment in HCC cells. Our results suggest that OA promotes the EMT process of HCC cells by inhibiting the activity of PP2A.

Single Nucleotide Polymorphisms of CBX4 and CBX7 Decrease the Risk of Hepatocellular Carcinoma.

BACKGROUND: The chromobox (CBX) proteins CBX2, CBX4, CBX6, CBX7, and CBX8, also known as Polycomb (Pc) proteins, are canonical components of the Polycomb repressive complex 1 (PRC1). Abundant evidence indicates that abnormal expression of Pc proteins is associated with a variety of tumors, but their role in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. In the present study, we performed a case-control study to investigate the relationship between single nucleotide polymorphisms (SNPs) of CBX genes and HCC. METHODS: Nine SNPs on CBX genes (rs7217395, rs2036316 of CBX2; rs3764374, rs1285251, rs2289728 of CBX4; rs7292074 of CBX6; and rs710190, rs139394, rs5750753 of CBX7) were screened and genotyped using MassARRAY technology in 334 HCC cases and 321 controls. The association between SNPs and their corresponding gene expressions was analyzed through bioinformatics methods using the Ensembl database and Blood eQTL browser online tools. RESULTS: The results indicated that rs2289728 (G>A) of CBX4 (P = 0.03, OR = 0.56, 95% CI: 0.33-0.94) and rs139394 (C>A) of CBX7 (P = 0.02, OR = 0.55, 95% CI: 0.33-0.90) decreased the risk of HCC. Interaction between rs2036316 and HBsAg increased the risk of HCC (P = 0.02, OR = 6.88, 95% CI: 5.20-9.11), whereas SNP-SNP interaction between rs710190 and rs139394 reduced the risk of HCC (P = 0.03, OR = 0.33, 95% CI: 0.12-0.91). Gene expression analyses showed that the rs2289728 A allele and the rs139394 A allele significantly reduced CBX4 and CBX7 expression, respectively. CONCLUSION: Our findings suggest that CBX4 rs2289728 and CBX7 rs139394 are protective SNPs against HCC. The two SNPs may reduce the risk of HCC while suppressing the expression of CBX4 and CBX7.

Downregulated Expression of Chromobox Homolog 7 in Hepatocellular Carcinoma.

Background: As an essential member of the Polycomb group (PcG) proteins, chromobox homolog 7 (CBX7) is found deregulated in some human cancers, and is thought to be a contributing factor in carcinogenesis. However, the expression and role of CBX7 in hepatocellular carcinoma (HCC) is still not well characterized. Materials and Methods: The levels of the CBX7 protein were quantified in 75 paired HCC and adjacent nontumor tissues by immunohistochemistry; comparisons were made using McNemar's chi-square test. The Kaplan-Meier estimate was used for survival analysis. Results: We found that the expression of CBX7 in HCC tissues was significantly lower than that of adjacent nontumor tissues. In addition, decreased CBX7 expression levels were correlated with liver cirrhosis in HCC patients. Furthermore, the survival times of HCC patients who were CBX7-expression-negative were shorter than HCC patients who were CBX7-expression-positive. Conclusion: Our results show that downregulation of CBX7 is related to HCC progression and a poor prognosis in HCC patients.

Correlations between chromobox homolog 8 and key factors of epithelial-mesenchymal transition in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in China, with high metastasis and poor prognosis. Recently, as the core component of the polycomb repressive complexes 1 (PRC1), chromobox protein homolog 8 (CBX8) is considered as an oncogene and prognostic marker in HCC. Methods: A tissue microarray of 166 paired HCC and adjacent non-tumor samples were collected to identify the relationship between CBX8 and epithelial mesenchymal transition (EMT) associated proteins by Spearman correlation analysis. Knock-down of CBX8 in HCC cells was conducted to detect the biologic functions of CBX8 in HCC metastasis. Results: We found out that CBX8 was over-expressed in HCC and its expression was closely related to the metastasis of HCC patients. In addition, knock-down of CBX8 was found to inhibit the invasion and migration ability of HCC cells. Moreover, there was a significant relationship between expression of CBX8 and EMT associated proteins both in HCC cells and tumor tissues. Conclusions: Our results indicate that CBX8 promotes metastasis of HCC by inducing EMT process.

Expression and Clinical Significance of CMTM6 in Hepatocellular Carcinoma.

This study aimed to examine the expression level and clinical significance of chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) in paired hepatocellular carcinoma (HCC) and adjacent nontumor tissues. The expression of CMTM6 was detected in 75 paired HCC and adjacent nontumor tissues by immunohistochemistry. Chi-square test was used to compare the difference of CMTM6 expression between HCC tissues and adjacent nontumor tissues. The clinic-pathological features and prognosis of HCC patients were collected to analyze the relationship with CMTM6 expression. The positive expression of CMTM6 in HCC tissues was significantly lower than that of adjacent nontumor tissues. The difference of CMTM6 expression between HCC tissues and paired adjacent nontumor tissues was statistically significant (p < 0.05). Furthermore, CMTM6 expression was correlated with HCC metastasis and alpha-fetoprotein (AFP) (p < 0.05). Multivariate logistic regression analysis showed tumor staging, metastasis, and AFP had a significant relationship with CMTM6 expression. In addition, the survival time of HCC patients was different between CMTM6 positive group and CMTM6 negative group by Kaplan-Meier survival analysis (p < 0.05). Downregulation of CMTM6 is related to HCC metastasis and the prognosis of HCC patients.