Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.

Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Mapping Tyrosine Kinases Based on a TK Activity-Representing Peptide Library Reveals a Role for SRC in H1975 Drug Resistance.

Tyrosine kinases (TKs) are prominent targets in cancer therapies, and more than 30 TK inhibitors have been approved for treatments in tumors with abnormal TK. Disappointingly, an incomplete response can occur with the long-term use of TK inhibitors, known as cancer drug resistance, which can be caused by kinome reprogramming. Hence, monitoring the status of TKs is crucial for revealing the underlying drug resistance mechanism. Here, we describe a TK activity-representing peptide library-based multiple reaction monitoring (TARPL-MRM) strategy for directly inferring TK activities. The strategy facilitated the assay of 87 human TKs through target quantification of 301 phosphorylation sites. Using this strategy, we demonstrated the heterogeneity of TK activity in different non-small cell lung cancer (NSCLC) cell lines and assessed the response of TK activities to the EGFR inhibitor AZD9291 in NSCLC cells. We found that the acquired resistance of H1975 cells to AZD9291 requires SRC activity, and inhibition of SRC plays potential roles in overcoming this resistance. In summary, our work reveals that this strategy has the potential to become a powerful tool for TK studies, clinical diagnostics, and the discovery of new therapeutic targets.

The association between sleep and empathy in young preschoolers: A population study.

Sleep is vital for children's early socio-emotional development, particularly empathy. This study aimed to explore the associations between sleep and empathy in young preschoolers. A sample of 23,259 preschoolers (4.3 ± 0.3 years) at the entry year of preschool was recruited as part of the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P) study. Caregivers reported on child sleep, affective empathy, and cognitive empathy through the Children's Sleep Habits Questionnaire and the Griffith Empathy Measure. Ordinary least-square regression and quantile regression were performed for the associations between sleep and empathy. Sex differences were also investigated. Night sleep duration was negatively associated with affective empathy (ß = -0.35, p < 0.001), and positively associated with cognitive empathy (ß = 0.41, p < 0.001). Longer nap duration was associated with higher affective empathy (ß = 0.28, p < 0.001). Sleep disturbances were positively associated with affective empathy (ß = 0.04, p < 0.001) and negatively associated with cognitive empathy (ß = -0.09, p < 0.001). These associations were generally stronger in children at higher empathy quantiles and also those at the 10th cognitive empathy quantile. The associations between sleep and affective empathy were mainly contributed by girls, and were more common in boys in terms of cognitive empathy, particularly at the 10th and the 30th quantiles. In conclusion, longer night sleep duration and fewer sleep disturbances are associated with a more mature empathy pattern in young preschoolers. The associations are more prominent in children at the higher end of the empathy spectrum, and vary by sex. These findings highlight the importance to promote sleep health in young children for optimal socio-emotional development.

Associations of CXCL12 polymorphisms with clinicopathological features in breast cancer: a case-control study.

BACKGROUND: Previous studies suggested that CXCL12 was involved in the development, metastasis, and invasion of breast cancer, and genetic variants were associated with the diagnosis and prognosis of patients with breast cancer. The present study was aimed to assess the relationships between CXCL12 polymorphisms (rs1801157, rs2297630, and rs2839693) and susceptibility and clinicopathological features of breast cancer. METHODS: A case-control study was conducted in 434 breast cancer patients and 450 health controls. Student t-test and chi-square test were used to analyze the differences of age distribution and genotype frequencies between the two groups. Correlations between polymorphisms and clinical parameters were also assessed by chi-square test. The potential effects of the three polymorphisms on CXCL12 were investigated by the public database. RESULTS: A statistical association was found between CXCL12 rs1801157 polymorphism and breast cancer risk, possibility of metastasis, and estrogen receptor status. Patients with rs2839693 C/T or C/T-T/T genotypes were more likely to be progesterone receptor-negative. However, no associations of rs2297630 polymorphism with breast cancer risk or any clinicopathological characteristics were observed. In addition, rs2297630 affected the splicing quantitative trait loci of CXCL12 in the subcutaneous fat, rs2839693 polymorphism affected the splicing quantitative trait loci of CXCL12 in the human breast mammary tissues. CONCLUSIONS: Those results indicated that CXCL12 polymorphisms might be potential diagnostic indicators, and more investigation is needed in the future.

How formal caregiver's BPSD knowledge influences positive aspects of caregiving: the mediating role of attitude and the moderating role of self-efficacy.

BACKGROUND: The current study investigated the relationship between behavioural and psychological symptoms of dementia (BPSD) knowledge and positive aspects of caregiving (PAC), in addition, how caregiving attitude and self-efficacy mediate or moderate this relationship. METHODS: Two hundred twenty-nine formal caregivers (51males and 178females) who has worked in nursing homes for more than a month were recruited.With a cross-sectional, face-to-face survey, structural questionnaires were implemented to evaluate formal caregiver's BPSD knowledge, attitude, self-efficacy and PAC.A 13-item self-developed questionnaire was used to assess caregiver's BPSD knowledge about disease characteristics, care and risks, and treatment needs. Dementia attitude, self-efficacy and positive aspects of caregiving were measured by dementia attitude scale, the General self-efficacy scale, and Chinese version of positive aspects of caregiving respectively. Model 5 in the PROCESS micro was employed in order to verify the mediating effect of attitude and the moderating effect of self-efficacy on the relationship between BPSD knowledge and PAC. RESULTS: The results showed that greater BPSD knowledge was associated with increased PAC, and this relationship was fully mediated by increased friendly attitude toward people with dementia. Moreover, direct effect was moderated by self-efficacy, and that only among those with high self-efficacy, the direct effect of BPSD knowledge was found on promoting PAC. CONCLUSIONS: By elucidating the knowledge-attitude-practice pathway in handling patient's BPSD, the current study extends existing literature and provides insights for developing psychoeducation programs among formal caregivers.

Identification of an immune-related RNA-binding protein signature to predict survival and targeted therapy responses in liver cancer.

RNA-binding proteins (RBPs) play crucial roles in multiple cancers. However, very few RBPs and their association with immune genes have been systematically studied in liver cancer (LC). We aimed to identify an immune-related RBP signature to predict the survival of LC patients. Bioinformatics methods were used to identify differentially expressed, immune-related, and prognostic RBPs and to develop an immune-related RBP signature based on data from the Cancer Genome Atlas (TCGA) cohort. We obtained eight differentially expressed, immune-related, and prognostic RBPs to construct a risk signature. The signature could effectively distinguish between high- and low-risk patients, and its predictive capacity was validated in the International Cancer Genomics Consortium (ICGC) cohort. We speculated that the high-risk group was more sensitive to targeted therapy. The immune-related RBP signature is an independent prognostic biomarker for LC patients and can expand the application of targeted therapy through patient stratification.

Estimating ecological sustainability in the Guangdong-Hong Kong-Macao Greater Bay Area, China: Retrospective analysis and prospective trajectories.

In recent decades, rapid urbanization and intensified global climate change have resulted in a significant difference of environment and resources distribution on space, which would cause trouble for accurate assessment of regional ecological sustainable development, especially in the large urban agglomerations. The parameters used in previous assessment methods have normally ignored spatial heterogeneity, leading to deviations in the evaluation accuracies against the context above. By incorporating remote sensing technology, this study proposed an improved emergy ecological footprint (EEF) method and a novel ecological sustainability index to comprehensively analyze the variability of ecological security states (ESS) from 1994 to 2018 in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) and to predict its sustainable growth potential based on a combined factorial decomposition and scenario analysis. Results showed that the pixel-based emergy analysis revealed significant heterogeneity over time and space under the impact of climate change and intense land use activities during the study period. The emergy carrying capacity per capita (ecc) and the emergy ecological footprint per capita (eef) also showed a significant difference between the nine cities in the GBA. In addition, the traditional EEF method, which does not consider the spatiotemporal variation, has indeed overestimated the GBA's ecc by 15% compared with our results. The ESS of the GBA gradually worsened from slight insecurity in the 1990s to moderate insecurity in 2018. If the current trends in socio-economic activities and climate change continue according to the RCP8.5 scenario in the IPCC, the ESS of the GBA will reach the extreme insecurity state in 2050. However, our scenarios show that industrial structure adjustment, energy structure optimization, and especially biological resource conservation can reduce the EFI by approximately 6.52%, 23.4%, and 30.6%, respectively. Consequently, effective implementation of the above measures can limit the increase both in emergy ecological deficit and emergy ecological footprint intensity (EFI) and, together, contribute to a higher security status in the GBA in 2050.

Cohort Profile: The Shanghai Sleep Birth Cohort Study.

BACKGROUND: Sleep disturbances in women occur frequently throughout pregnancy. Previous studies have demonstrated that the increasing incidence of physiological and psychological illness is concurrent with increasing sleep deprivation and poor sleep quality in adults and children. OBJECTIVES: The Shanghai Sleep Birth Cohort Study (SSBCS) was established to examine the effect of sleep disturbances during the third trimester on emotional regulation of mothers; to assess the effect of maternal sleep during pregnancy on the growth and development of children; and to explore the influence of children's sleep characteristics on physical and social-emotional development. POPULATION: The study was conducted in the Renji Hospital in Pudong New District, Shanghai from May 2012 to July 2013. Women and their newborns who met the inclusion criteria and agreed to participate in this study were recruited to the SSBCS. METHODS: The follow-up visits for children were conducted at the age of 42 days, 3, 6, 9, 12, 18, and 24 months, and 3, 4, and 6 years. Data on demographic factors, physical examination, sleep assessment, developmental and psychiatric assessment, diet records, and biological samples were collected throughout the study. PRELIMINARY RESULTS: A total of 277 pregnant women were recruited to the study; the response rate was 64.3%. 37.9% of the pregnant women had poor sleep quality and 12.0% suffered from depression. Infant sleep patterns changed during the first year of life, but most sleep characteristics showed little variation from 6 to 12 months. CONCLUSIONS: The SSBCS is an on-going prospective cohort study with follow-up to 6 years. The detailed data on demographic factors, sleep assessment, physical examinations, neurodevelopmental and psychiatric assessment, diet records, and biological samples make this research platform an important resource for examining the potential effects of sleep characteristics on both maternal and child health.

Combined effects of weight change trajectories and eating behaviors on childhood adiposity status: A birth cohort study.

Previous studies have suggested that infant rapid weight change can be associated with an increased weight later in life. However, the weight change trajectory in early life over time and which childhood lifestyle behaviors may modify the risk of rapid weight change have not been characterized. Using our ongoing birth cohort study, we have addressed these issues. Nine follow-up time points (birth, 3, 6, 9, 12, 18, 24, 36, and 48 months) were used to calculate the change between two adjacent weight-for-age z-scores (WAZ-change), and then WAZ-change trajectories were defined via group-based trajectory modeling. The solitary, independent and combined effects of WAZ-change trajectories and each lifestyle factor (eating behaviors, physical activity, media exposure time and total sleep duration) on childhood adiposity measures at age 4 years were determined using multivariate regression analysis. Overall, 84 (38%) children had a steady growth trajectory from birth to 4 years, while the other 137 (62%) children had an early infancy rapid growth trajectory, particularly in the first three months. Compared to children with steady growth, children with early infancy rapid growth had a significantly higher body mass index, waist circumference, and subcutaneous fat. Moreover, weight change trajectory and three eating behaviors (i.e. food responsiveness, satiety responsiveness and food fussiness), not only had independent effects, but also combined (synergistic) effects on the majority of adiposity measures. Our results extend the current literature and provide a potentially valuable model to aid clinicians and health professionals in designing early-life interventions targeting specific populations, specific ages and specific lifestyle behaviors to prevent childhood overweight/obesity.

Incidence and disease burden of prostate cancer from 1990 to 2017: Results from the Global Burden of Disease Study 2017.

BACKGROUND: The patterns of the incidence and mortality of prostate cancer (PC) have been changing over the years. In addition, the unclear etiology of PC necessitates further studies into the geographic distribution and age composition of patients with PC. This study was aimed at examining the patterns of the epidemiology of PC to help policymakers to allocate the limited resources of the health care system accordingly. METHODS: Annual case data and age-standardized rates (ASRs) were obtained for the incidence, mortality, and disability-adjusted life-years (DALYs) of PC according to age from 1990 to 2017 and for 21 regions, including 195 countries and territories. The estimated annual percentage changes (EAPCs) of ASRs were calculated to evaluate the incidence and mortality trends of PC. RESULTS: Worldwide, the age-standardized incidence rate (ASIR) of PC increased from 30.5 cases per 100,000 population in 1990 to 37.9 cases per 100,000 population in 2017 with an EAPC of 0.59 (95% confidence interval [CI], 0.49-0.7), whereas the mortality decreased with an EAPC of -0.73 (95% CI, -0.80 to -0.67). The ASIR was positively associated with the sociodemographic index (SDI) in most regions, and the increase in the ASIR was steeper with a higher SDI. The proportion of patients younger than 65 years increased from 23.6% in 1990 to 27.3% in 2017. CONCLUSIONS: The incidence of PC has been increasing globally, whereas its mortality and DALYs have been decreasing. These trends are particularly significant in developed regions and vary across geographic regions. Adjustments to the medical strategy by governments and medical institutions are required.

The Prognostic Value of the Number of Negative Lymph Nodes Combined with Positive Lymph Nodes in Esophageal Cancer Patients: A Propensity-Matched Analysis.

BACKGROUND: Currently, the number of negative lymph nodes (NLNs) has been paid increasing attention and is considered a prognostic indicator in diverse cancers. Therefore, it is necessary to explore the association between number of NLNs and prognosis in esophageal cancer (EC) patients. METHODS: Our data were obtained from the Surveillance, Epidemiology, and End Results 18 database. The X-tile plot was used to determine the optimal cut-off value of the number of NLNs, and propensity score matching (PSM) was performed according to the results of the X-tile plot. RESULTS: A total of 4777 patients were eligible, and 882 pairs of patients were included after PSM. The result of the X-tile plot revealed an optimal cut-off value of three NLNs. Multivariate Cox regression analysis revealed better EC-specific survival (ECSS) in patients with more than three NLNs (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.59-0.77; p < 0.001) compared with patients with three or fewer NLNs. A subgroup analysis revealed better ECSS in patients with more than three NLNs with one to two (HR 0.57, 95% CI 0.46-0.71; p < 0.001) or three to six (HR 0.68, 95% CI 0.50-0.92; p = 0.012) positive lymph nodes (PLNs). CONCLUSIONS: More than three NLNs is associated with better survival in EC patients, especially when the number of PLNs is one to two or three to six. We confirm that the combination of the number of NLNs and number of PLNs can provide better prognostic guidance for EC.

LncRNA MEG3 rs3087918 was associated with a decreased breast cancer risk in a Chinese population: a case-control study.

BACKGROUND: LncRNA MEG3 expressed abnormally in various cancers including breast cancer, but no studies reported the correlation between MEG3 SNPs and breast cancer susceptibility among Chinese women. METHODS: This study is aimed to explore the association between three SNPs of MEG3 (rs3087918, rs7158663, rs11160608) and breast cancer. The study is a population-based case-control study including 434 breast cancer patients and 700 healthy controls. Genotyping was performed using Sequenom MassArray technique. Function prediction of rs3087918 were based on RNAfold and lncRNASNP2 databases. RESULTS: Pooled analysis indicated that rs3087918 was related to a decreased risk of breast cancer [GG vs. TT: OR (95%) = 0.67(0.45-0.99), P = 0.042; GG vs. TT + TG: OR (95%) = 0.69(0.48-0.99), P = 0.046], especially for women aged <=49 [GG vs. TT: OR (95%) = 0.40(0.22-0.73), P = 0.02]. Comparison between case groups showed genotype GG and TG/GG of rs3087918 were associated with her-2 receptor expression [GG vs. TT: OR (95%) = 2.37(1.24-4.63), P = 0.010; TG + GG vs. TT: OR (95%) = 1.50(1.01-2.24), P = 0.045]. We didn't find statistical significance for rs11160608, rs7158663 and breast cancer. Structure prediction based on RNAfold found rs3087918 may influence the secondary structure of MEG3. The results based on lncRNASNP2 indicated that rs3087918 may gain the targets of hsa-miR-1203 to MEG3, while loss the target of hsa-miR-139-3p and hsa-miR-5091 to MEG3. CONCLUSIONS: MEG3 rs3087918 was associated with a decreased risk of breast cancer. MEG3 haplotype TCG may increase the risk of breast cancer.

Explicit Spatializing Heat-Exposure Risk and Local Associated Factors by coupling social media data and automatic meteorological station data.

Extremely high temperatures, a major cause for weather-related public health issues, are projected to intensify and become more frequent. To mitigate the adverse effects, a low-cost and effective risk assessment method should be developed. Therefore, we applied automatic meteorological station data and population mobility data to develop a high spatiotemporal resolution temperature risk assessment method. The population mobility analysis results showed the working/residential complex pattern in Tianhe District, with hotspots of spatial clustering located in the north, southwest, and southeast of the study area. Taking the population mobility patterns into consideration, high-temperature risk assessment results with a resolution of 100 m were obtained. The total mortality cases in 2014 and 2015 were used to validate this result. The validation showed that the total mortality in the high-temperature risk areas accounted for over 36% of that in Tianhe District. Thus, the method introduced in this study is capable of reflecting weather-related risk. Furthermore, the high-temperature risk assessment results showed that most of the risky areas were located in the southwest of the study area. Two peak times of the risk areas were determined, being before dawn and in the evening. Compared with the risk areas during weekdays, those at weekends expanded. In addition, we used the geographically weighted regression model to investigate the potential influencing factors. Individual factor contributed more than 22.4% to the spatial distribution of heat exposure. Catering services, transportation services, and living services were higher than others, with mean R2 values of 0.28, 0.23, and 0.25, respectively. More than 47.9% of spatial distribution of heat exposure was attributed to joint function of influencing factors, with global R2 ranged from 0.23 to 0.34. Our research introduces a spatial-specific method to quantitatively assess high-temperature risk. Moreover, the mechanisms behind the spatial distribution of the high-temperature risk were discussed. The theoretical and management implications can help urban designers and energy governors to develop useful strategies to mitigate weather-related public health risks.

[Progress on formation and taste-masking technology of stench of animal medicines].

Animal medicines have been called "medicine with affinity to flesh and blood" by doctors of all ages, which always act as an important branch of Chinese medicine. They have various types, extensive sources and long application history, with unique cli-nical effects in anti-coagulation, anti-thrombosis, anti-fatigue, immune regulation, anti-tumor, anti-convulsion and so on. Most animal medicines contain proteins, fatty acids, and trimethylamine oxides, which are prone to decomposition and produce substances such as biological amines, aldehydes, ketones, alcohols, trimethylamine and ammonia with unpleasant odors. The stench produced by the combination of various odors can easily cause side effects such as nausea and vomiting, which would probably affect the drug compliance and clinical efficacy in patients, and block the development of high-quality animal medicines. At present, we have insufficient understanding on sources and formation mechanism of the stench of animal medicines, lacking development of taste-masking technology. Therefore, the universality, formation, vomiting mechanism, evaluation methods, and masking technology of stench of animal medicines were summarized in this paper, so as to deepen the recognition of stench, provide references for the development of animal medicines deodorization technology, enhance patients' compliance with animal medicines, and promote animal drugs to better serve public health in the new era.

Scutellarin inhibits proliferation and invasion of hepatocellular carcinoma cells via down-regulation of JAK2/STAT3 pathway.

The prognosis of hepatocellular carcinoma (HCC) is poor because of high incidence of recurrence and metastasis. JAK/STAT signalling pathway regulates cell proliferation, apoptosis, differentiation and migration and epithelial-mesenchymal transition (EMT) is also considered to contribute to invasion and metastasis of epithelial malignant tumours. Scutellarin is an active component found in many traditional Chinese herbs and has been regularly used in anti-inflammatory and antitumour medicine. This study aimed to identify the effect of scutellarin and its possible mechanism of action in HCC cells. Proliferation, colony-forming, apoptosis and cell migration assays were used to examine the effect of scutellarin on HCC cells. Quantitative real-time PCR and Western blotting were performed to study the molecular mechanisms of action of scutellarin. Light and electron microscopy and immunofluorescence analysis were performed to study the effect of scutellarin on cellular mechanics. We show that scutellarin potentially suppresses invasiveness of HepG2 and MHCC97-H cells in vitro by remodelling their cytoskeleton. The molecular mechanism behind it might be the inhibition of the EMT process, which could be attributed to the down-regulation of the JAK2/STAT3 pathway. These findings may provide new clinical ideas for the treatment of liver cancer.

Hyperuricemia and gout are associated with cancer incidence and mortality: A meta-analysis based on cohort studies.

The association between hyperuricemia or gout and cancer risk has been investigated in various published studies, but their results are conflicting. We conducted a meta-analysis to investigate whether hyperuricemia or gout was associated with the cancer incidence and mortality. Linear and nonlinear trend analyses were conducted to explore the dose-response association between them. The pooled relative risk (RR) and 95% confidence interval (CI) were used to evaluate cancer risk. A total of 24 articles (33 independent studies) were eligible for inclusion. When compared participants with the highest SUA (hyperuricemia) levels and those with the lowest SUA levels, the pooled RR was 1.08 (95% CI, 1.04-1.12), it was significantly associated among males but not among females (males, RR = 1.07; 95% CI, 1.03-1.11; females, RR = 1.06; 95% CI, 0.96-1.17). Hyperuricemia increased total cancer mortality (RR = 1.15; 95% CI, 1.05-1.26), but a significant association was observed in females rather than in males (females: RR = 1.26; 95% CI, 1.09-1.45; males, RR = 1.02; 95% CI, 0.80-1.30). Linear relationships of SUA levels with overall cancer incidence (p for nonlinearity = 0.238) and overall cancer mortality (p for nonlinearity = 0.263) were identified. However, 1 mg/dL increment in SUA levels was weakly significant in overall cancer incidence (RR = 1.01; 95% CI, 1.01-1.01) but not associated with overall cancer mortality (RR = 1.01; 95% CI, 0.99-1.03). Gout was significantly associated with increased cancer incidence (RR = 1.19; 95% CI, 1.12-1.25). In conclusion, Hyperuricemia or gout was associated with higher cancer incidence and mortality. Though a potential linear relationship between them was found, we'd better treat this result with caution.

Impact of four lncRNA polymorphisms (rs2151280, rs7763881, rs1136410, and rs3787016) on glioma risk and prognosis: A case-control study.

Long noncoding RNA (lncRNA) polymorphisms are reportedly in connection with tumor susceptibility and prognosis. Glioma is one of the most aggressive and common cancers of the central nervous system. This study aimed to investigate the relationship between four lncRNA variants and glioma susceptibility and prognosis in a Chinese Han population. Sequenom Mass-ARRAY was used to genotype 605 patients with glioma and 1300 cancer-free individuals. Odds ratios or hazard ratios and related 95% confidence intervals were calculated to estimate the correlations. Logistic and Cox regression models, log-rank tests, and Kaplan-Meier curves were used for the statistical analysis. Six inheritance models showed that ANRIL rs2151280 variant genotype (A>G) was related to the susceptibility of glioma, while the other three lncRNAs showed no association. Patients treated with temozolomide or nimustine had better progression-free survival (PFS) and overall survival (OS) than those treated with platinum. Besides, patients aged older than 40 years showed a poorer OS. The Cox multivariate analysis revealed that the rs1136410 GG genotype (A>G) was beneficial for OS and PFS. The Kaplan-Meier analyses indicated that rs1136410 A>G and the rs7763881 A>C were associated with longer OS. ANRIL rs2151280 variant genotype might increase susceptibility of glioma. In addition, PARP1 rs1136410 variant genotype could be beneficial for the overall survival of patients with glioma. More research data are needed to further validate our results.

GSTM1 and GSTT1 null genotype increase the risk of hepatocellular carcinoma: evidence based on 46 studies.

BACKGROUND: It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC. METHODS: We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0). RESULTS: The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18-1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23-1.66) increased the risk of HCC. And GSTM1-GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22-2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22-1.71), GSTT1 null OR = 1.48, 95% CI = (1.25-1.77), GSTM1-GSTT1 null OR = 1.58, 95% CI = (1.19-2.09), while we didn't obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1-GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null. CONCLUSIONS: Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1-GSTM1 dual-null genotypes is more likely to develop HCC.

Genetic polymorphisms of estrogen receptor genes are associated with breast cancer susceptibility in Chinese women.

BACKGROUND: Estrogen exposure is a widely known risk factor for BC. And the interaction of estrogen with estrogen receptor (ER) plays an important role in breast cancer development. This case-control study aims to assess the association of genetic polymorphisms in the estrogen receptor genes with breast cancer (BC) susceptibility in Chinese Han women. METHODS: Four polymorphisms (rs2881766, rs9383951, rs9340799 in ESR1 and rs3020449 in ESR2) were genotyped in 459 patients and 549 healthy controls using the Sequenom MassARRAY method. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the associations. False-positive report probability (FPRP) was utilized to examine the noteworthiness of significant findings. RESULTS: We observed that rs2881766 was associated with a decreased BC risk (GG vs. TT: OR = 0.63, 95% CI = 0.44-0.91; GG vs. TT/GT: OR = 0.68, 95% CI = 0.49-0.95), while rs3020449 was associated with an increased risk of BC (CT vs. TT: OR = 1.58, 95% CI = 1.21-2.06; CT/CC vs. TT: OR = 1.54, 95% CI = 1.20-1.98; TT/CC vs. CT: OR = 1.48, 95% CI = 1.15-1.90). The other two polymorphisms have no relation with BC susceptibility. In addition, rs2881766 was correlated with lymph node metastasis and ER expression, and rs3020449 was related to tumor size, histological grade and ER expression. The values of false-positive report probability indicated that the significant associations of BC risk with both rs2881766 and rs3020449 were noteworthy. CONCLUSIONS: Our study suggests that polymorphisms rs2881766 and rs3020449 in estrogen receptor genes were associated with BC susceptibility as well as clinical features in Chinese women. These findings need further validation in a large population.

Identification of long non-coding RNA signatures in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and lack of targets for therapy. This study aimed to explore the expression profile and potential function of lncRNAs in TNBC through bioinformatic methods. METHODS: Two microarrays of TNBC were obtained from the Gene Expression Omnibus database. Differentially expressed lncRNAs and mRNAs were screened out and the expressions of top lncRNAs and overlapping lncRNAs were validated using data from The Cancer Genome Atlas database. The co-expression analysis of lncRNAs and mRNAs was conducted using R software and functional enrichment analysis for was performed by Metascape. Kaplan-Meier Plotter was used for survival analysis. RESULTS: A total of 1034 dysregulated lncRNAs were found in the two microarrays, and there were 8 overlapped lncRNAs. Among them, 537 lncRNAs were significantly correlated with 451 protein-coding genes (PCGs). The co-expressed PCGs were mainly enriched in terms including cell division, cell cycle, and protein/DNA binding, and were involved in pathways in cancer and other pathways such as PI3K-Akt, MAPK, ErbB and p53 signaling pathways. Hub-genes in the co-expression network were identified, and 7 of them were associated with relapse-free survival of TNBC (MAGI2-AS3: HR = 0.51; GGTA1P: HR = 0.54; NAP1L2: HR = 0.59; CRABP2: HR = 0.41; SYNPO2: HR = 0.50; MKI67: HR = 2.23; COL4A6: HR = 1.91; all P < 0.05). CONCLUSIONS: Numerous lncRNAs were dysregulated in TNBC, and many of them are possibly involved in cancer biology. Several of these lncRNAs were associated with of TNBC prognosis, which can be promising biomarkers.