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Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case–control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (Ptrend < 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T>C reduced the stability of E2F2 3’-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e−8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02–1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3, and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells.

The 1‐year mortality and health consequences of COVID‐19 in cancer patients are relatively underexplored. In this multicenter cohort study, 166 COVID‐19 patients with cancer were compared with 498 non‐cancer COVID‐19 patients and 498 non‐COVID cancer patients. The 1‐year all‐cause mortality and hospital mortality rates in Cancer COVID‐19 Cohort (30% and 20%) were significantly higher than those in COVID‐19 Cohort (9% and 8%, both P

Background The study aim was to investigate one-year all-cause mortality and health consequences of cancer COVID-19 patients in China, stratified by primary tumor subtype. Methods In this multicenter cohort study, 166 cancer COVID-19 patients were studied along with 498 gender- and age-matched non-cancer COVID-19 patients in four hospitals in Wuhan, China, admitted 2020/01/01-2020/03/18, as well as with 498 parallel gender-, age-, and cancer subtype- matched non-COVID cancer patients hospitalized between 2019/01/01-2020/03/17. All patients were followed-up with a telephone survey to assess health consequences. Cox proportional hazards regression were used for risk analysis. Results In the three cohorts of median age of 65 ± 1 year and 49% male, the one-year all-cause mortality and hospital mortality rates of Cancer COVID-19 Cohort, 30% and 20% respectively, were significantly higher than COVID-19 Cohort (9% and 8%), and Cancer Cohort (16% and 2%). The 12-month all-cause post-discharge mortality rate of Cancer COVID-19 Cohort (11%) was higher than COVID-19 Cohort (0.4%), but similar to Cancer Cohort (15%). The high 1-year all-cause mortality was among hematologic malignancies (65%) and then nasopharyngeal, brain and skin tumors (45%), digestive system (43%), and lung (32%). the rate was low among genitourinary (14%), female genital (13%), breast (11%), and thyroid (0). As for patients having at least one symptom at the 1-year follow-up, Cancer COVID-19 Cohort (23%, 26/114) is similar to COVID-19 Cohort (30%, 130/432). Discussion Cancer COVID-19 patients showed a high rate of hospitalization mortality, but not after discharged, signifying the strong acute adverse effect of COVID-19 on cancer patients while little was in long-term effect. Risk stratification showed that hematologic malignancies, nasopharyngeal, brain, digestive system and lung tumors were high risk, while genitourinary, female genital, breast and thyroid were low risk which was similar to non-cancer COVID-19. Conclusions COVID-19 had little effect of 1-year mortality and sequelae for cancer survivors discharged from SARS-CoV-2 virus infection. Different tumor subtypes had different effect of COVID-19. COVID-19 patients with thyroid, breast, female genital, genitourinary tumor had low risk mortality which was similar to non-cancer patients.

The simulation of overland flow, wherein runoff yield and concentration are influenced by topography, is fundamental to hydrological forecasting. Therefore, critically evaluating the characteristics of overland flow under the influence of topographic depressions—which are one of the most common microtopographic structures—is vital for improving current hydrological models. In this study, we developed a solution for the real-world application of overland flow simulations under the influence of depressions in hydrological models. A relative depression storage–outflow curve (RDOC) was proposed to investigate surface outflow processes. Experiments were conducted based on the variable-controlling approach using three rainfall return periods, four slopes, and four depression rates while ensuring a consistent initial soil moisture content. A homogenized RDOC was achieved based on shape analysis; it was parameterized by the outflow threshold and the reciprocal of the curve index of two outflow stages (B and D). A relative depression storage–outflow function (RDOF) was generated and a complete calculation procedure was applied within a hydrological model. Furthermore, we analyzed the hydrological responses to parameters of different hydrological factors to improve our understanding of the parameter determination of the RDOF.

// Ying Yuan 1, 2, * , Hua Zhang 2, 3 , Xuexia Liu 4, * , Zhongming Lu 5 , Guojun Li 2, 6 , Meixia Lu 7 and Xiaofeng Tao 1 1 Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 2 Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA 3 Department of Otolaryngology-Head and Neck Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China 4 Department of Central Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China 5 Department of Otolaryngology-Head and Neck Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China 6 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA 7 Department of Epidemiology and Biostatistics and The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * These authors have contributed equally to this work and are considered co-first authors Correspondence to: Xiaofeng Tao, email: cjr.taoxiaofeng@vip.163.com Meixia Lu, email: mlu@hust.edu.cn Keywords: glioblastoma multiforme, microRNA, prognosis, overall survival, TCGA Received: February 07, 2017 Accepted: March 14, 2017 Published: April 06, 2017 ABSTRACT MicroRNAs (miRNAs) play major roles in various biological processes and have been implicated in the pathogenesis and malignant progression of glioblastoma multiforme (GBM). The aim of this study was to assess the predictive values of miRNAs for overall survival (OS) of patients with GBM. MiRNA expression profiles and clinical information of 563 GBM patients were obtained from the Cancer Genome Atlas. The most significantly altered miRNAs were identified and miRNA expression profiles were performed, through principal component analysis, the least absolute shrinkage and selection operator method. The survival analysis was performed using the Cox regression models. Additionally, receiver operating characteristic (ROC) analysis was used to assess the performance of survival prediction. We used the bioinformatics tools to establish the miRNA signature for biological relevance assessment. A linear prognostic model of three miRNAs was developed and the patients were divided into high risk and low risk groups based this model. The area under the ROC curve (AUC) for the three miRNA signature predicting 5-year survival was 0.894 (95%CI, 0.789-1.000) in the testing set and0.841 (95%CI, 0.689-0.993) in all GBM patients. High risk patients had significantly shorter OS than patients with low risk ( P < 0.001). The results from this study support a three miRNA signature for outcome prediction of GBM. These results provided a new prospect for prognostic biomarker of GBM.

Given roles of HPV and genetic factors in cancer risk, we evaluated associations of HPV16 seropositivity and five E2F2 promoter variants with squamous cell carcinoma of oropharynx (SCCOP) and squamous cell carcinoma of oral cavity (SCCOC) risk in a case-control study of 325 patients and 335 cancer-free matched controls. We found that HPV16 seropositivity was significantly associated with SCCOP risk (aOR, 5.4, 95%CI, 3.7-8.9) but not SCCOC (aOR, 0.8, 95%CI, 0.4-1.5), while each E2F2 polymorphism had no significant main effect on SCCOP and SCCOC risk. However, after combining HPV serological status and E2F2 promoter variants together, the modification effect of HPV serology and individual or combined risk genotypes of five polymorphisms on risk was significantly higher among SCCOP than among SCCOC. Furthermore, the stratified analysis by smoking status showed that all such modifying effects aforementioned on SCCOP were more pronounced in never smokers than in smokers. These findings are in agreement with those of previous studies, in which a majority of SCCOP were caused by HPV infection, whereas most SCCOC were found to be caused by smoking and drinking. Taken together, these findings indicate that the risk of SCCOP as opposed to SCCOC associated with HPV16 seropositivity was modified by E2F2 promoter variants either individually or jointly, especially in never smokers.

// Hao Shi 1 , Jian Chen 3 , Yuncheng Li 2 , Guojun Li 4 , Rong Zhong 1 , Dandan Du 1 , Ruiwei Meng 1 , Weijia Kong 2 , Meixia Lu 1 1 Department of Epidemiology and Biostatistics, and The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 2 Department of Otorhinolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 3 Department of Head and Neck Surgery, Hubei Cancer Hospital, and Hubei Key Laboratory of Medical Information Analysis & Tumor Diagnosis and Treatment, Wuhan, Hubei, China 4 Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence to: Meixia Lu, e-mail: mlu@hust.edu.cn Weijia Kong, e-mail: entwjkong@hust.edu.cn Keywords: HNSCC, miRNA, prognosis, overall survival, TCGA Received: January 10, 2016 Accepted: February 20, 2016 Published: February 27, 2016 ABSTRACT The 5-year survival rate of patients with head and neck squamous cell carcinoma (HNSCC) was only 40%-50%. To investigate the prognostic and predictive value of specific mircoRNAs (miRNAs) in HNSCC. We identified 19 miRNAs associated with over survival (OS) of patients with HNSCC in different clinical classes between 492 HNSCC tissues and 44 normal tissues from The Cancer Genome Atlas (TCGA) dataset. A signature of six miRNAs was identified by the supervised principal component method in the training set. The AUC of the ROC curve for the six microRNA signature predicting 5-year survival was 0.737 (95%CI, 0.627-0.825) in the testing set and 0.708 (95%CI, 0.616-0.785) in the total dataset. In the multivariate Cox regression analysis, patients with high-risk scores had shorter OS (HR, 2.380, 95%CI, 1.361-4.303) than patients with low-risk scores in the total dataset. Therefore, these results provided a new prospect for prognostic biomarker of HNSCC.

In this study, we evaluated the clinical diagnostic value of vestibular evoked myogenic potentials (VEMPs) for endolymphatic hydrops (EH) by systematic review and Meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under summary receiver operating characteristic curves (AUC) were calculated. Subgroup analysis and publication bias assessment were also conducted. The pooled sensitivity and the specificity were 49% (95% CI: 46% to 51%) and 95% (95% CI: 94% to 96%), respectively. The pooled positive likelihood ratio was 18.01 (95% CI: 9.45 to 34.29) and the pooled negative likelihood ratio was 0.54 (95% CI: 0.47 to 0.61). AUC was 0.78 and the pooled diagnostic odds ratio of VEMPs was 39.89 (95% CI: 20.13 to 79.03). In conclusion, our present meta-analysis has demonstrated that VEMPs test alone is not sufficient for Meniere’s disease or delayed endolymphatic hydrops diagnosis, but that it might be an important component of a test battery for diagnosing Meniere’s disease or delayed endolymphatic hydrops. Moreover, VEMPs, due to its high specificity and non-invasive nature, might be used as a screening tool for EH.

The RAS association domain family protein 1a (RASSF1A), a tumor suppressor gene at 3p21.3, plays a very important role in various cancers, including the head and neck squamous cell carcinoma (HNSCC). Hypermethylation of CpG islands in the RASSF1A promoter region contribute to epigenetic inactivation. However, the association between RASSF1A promoter methylation and HNSCC remains unclear and controversial. Therefore, a meta-analysis was performed in the study to identify the association. We identified the eligible studies through searching PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure (CNKI) databases with a systematic searching strategy. The information on characteristics of each study and prevalence of RASSF1A methylation were collected. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Meta-regression was performed to analyze heterogeneity and funnel plots were applied to evaluate publication bias. A total of 550 HNSCC patients and 404 controls from twelve eligible studies were included in the meta-analysis. Overall, a significant association was observed between RASSF1A methylation status and HNSCC risk under a random-effects model (OR = 2.93, 95% CI: 1.58–5.46). There was no significant publication bias observed. The meta-analysis suggested that there was a significant association between aberrant RASSF1A methylation and HNSCC.

Background The p16INK4a is an important tumor suppressor gene (TSG) and aberrant methylation of promoter is known to be a major inactivation mechanism of the tumor suppressor and tumor-related genes. Aberrant TSG methylation was considered an important epigenetic silencing mechanism in the progression of head and neck squamous cell carcinoma (HNSCC). However, some studies have reported differences in the methylation frequencies of P16INK4a promoter between cancer and the corresponding control group. Therefore, we conducted a meta-analysis to better identify the association. Methods PubMed, Ovid, ISI Web of Science, and EMBASE were searched to identify eligible studies to evaluate the association of p16INK4a promoter methylation and HNSCC. Odds ratio (ORs) and 95% confidence intervals (95%CI) were calculated to evaluate the strength of association between p16INK4a promoter methylation and HNSCC. Results A total of twenty-one studies with 1155 cases and 1017 controls were included in the meta-analysis. The frequencies of p16INK4a promoter methylation in the cancer group were significantly higher than those in the control group (cancer group: median: 46.67%, range = 7.84%-95.12%; control group: median: 18.37%, range = 0–83.33%; respectively). The pooled odds ratio was 3.37 (95%CI = 2.32–4.90) in the cancer group versus the corresponding control group under the random-effects model. Conclusion This meta-analysis of 21 published studies identified that aberrant methylation of p16INK4a promoter was found to be significantly associated with HNSCC.

The purpose of this survey was to determine the association of parents’ attitudes and behaviors toward children's visual care with myopia risk in school-aged children. A total of 894 parents of school-aged children were investigated in primary and middle schools in the central and noncentral urban area in Wuhan through stratified cluster random sampling on July, 2015. We analyzed the association by the generalized linear mixed model. The results indicated that children with parents’ high expectations of 1.5 or higher on their vision exhibited a decreased risk of myopia compared with 1.0 and 0.5 or lower (OR = 0.49, 95%CI = 0.36–0.67). Children whose parents only paid attention to their vision in junior and senior school and in primary school had an increased myopia risk than that in preschool (OR = 2.12, 95%CI = 1.01–4.45, and OR = 3.11, 95%CI = 1.28–7.58, respectively). Children whose parents ensured for their sufficient sleep had a decreased myopia risk (OR = 0.45, 95%CI = 0.24–0.85). Compared with children whose parents who never adjusted electronic devices’ parameters, the odds ratio of sometimes was 0.49 (95%CI = 0.31–0.79), often 0.53 (95%CI = 0.33–0.85), and always 0.44 (95%CI = 0.26–0.75), respectively. Parents’ attitudes and behaviors toward children's visual care are significantly associated with the myopia risk in school-aged children. Consequently, efforts should be made to educate parents on how they protect children's vision and reduce their risk of myopia.

BACKGROUND: Death-associated protein kinase1 (DAPK1) is an important tumor suppressor gene. DNA methylation can inactivate genes, which has often been observed in the carcinogenesis of cervical cancer. During the past several decades, many studies have explored the association between DAPK1 promoter methylation and cervical cancer. However, many studies were limited by the small samples size and the findings were inconsistent among them. Thus, we conducted a meta-analysis to assess the association between DAPK1 promoter methylation and cervical cancer. METHODS: We systematically searched eligible studies in the PubMed, Web of Science, EMBASE and CNKI databases. Using meta-regression, subgroup analysis and sensitivity analysis, we explored the potential sources of heterogeneity. The odds ratio (OR) and 95% confidence interval (95% CI) were calculated by Meta-Analysis in R. RESULTS: A total of 15 studies from 2001 to 2012, comprising 818 tumor tissues samples and 671 normal tissues samples, were analyzed in this meta-analysis. The frequencies of DAPK1 promoter methylation ranged from 30.0% to 78.6% (median, 59.3%) in cervical cancer tissue and 0.0% to 46.7% (median, 7.8%) in normal cervical tissue. The pooled OR was 19.66 (95%CI = 8.72-44.31) with the random effects model, and heterogeneity was found through the sensitivity analysis. The I2 = 60% (P = 0.002) decreased to I2 = 29.2% (P = 0.144) when one heterogeneous study was excluded, and the pooled OR increased to 21.80 (95%CI = 13.44-35.36) with the fixed effects model. CONCLUSION: The results suggested a strong association between DAPK1 promoter methylation and cervical cancer. This study also indicated that DAPK1 promoter methylation may be a biomarker during cervical carcinogenesis that might serve as an early indication of cervical cancer.

Background The RAS association domain family protein 1a gene (RASSF1A) is one of the tumor suppressor genes (TSG). Inactivation of RASSF1A is critical to the pathogenesis of cancer. Aberrant TSG methylation was considered an important epigenetic silencing mechanism in the progression of ovarian cancer. A number of studies have discussed association between RASSF1A promoter methylation and ovarian cancer. However, they were mostly based on a small number of samples and showed inconsist results, Therefore, we conducted a meta-analysis to better identify the association. Methods Eligible studies were identified by searching the PubMed, EMBASE, Web of Science, and CNKI databases using a systematic searching strategy. We pooled the odds ratio (ORs) from individual studies using a fixed-effects model. We performed heterogeneity and publication bias analysis simultaneously. Results Thirteen studies, with 763 ovarian cancer patients and 438 controls were included in the meta-analysis. The frequencies of RASSF1A promoter methylation ranged from 30% to 58% (median is 48%) in the cancer group and 0 to 21% (median is 0) in the control group. The frequencies of RASSF1A promoter methylation in the cancer group were significantly higher than those in the control group. The pooled odds ratio was 11.17 (95% CI = 7.51–16.61) in the cancer group versus the corresponding control group under the fixed-effects model. Conclusion The results suggested that RASSF1A promoter methylation had a strong association with ovarian cancer.

Deregulated expression of most members of the E2F family has been detected in many human cancers. We examined the association of common single nucleotide polymorphisms (SNPs) of E2F transcription factors 1 and 2 (E2F1 and E2F2) with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,096 SCCHN patients and 1,090 cancer-free controls. We genotyped 10 selected SNPs in E2F1 and E2F2, including those at the near 5'-untranslated region (UTR), microRNA (miRNA)-binding sites at the near 3'-UTR and tagSNPs according to bioinformatics analysis. Although none of the selected SNPs alone was significantly associated with risk of SCCHN, there was a statistically significantly increased risk of SCCHN associated with the combined risk genotypes (i.e., rs3213182 AA, rs3213183 GG, rs3213180 GG, rs321318121 GG, rs2742976 GT+TT, rs6667575 GA+AA, rs3218203 CC, rs3218148 AA, rs3218211 CC, and rs3218123 GT+TT). Compared with those with 0-4 risk genotypes, an increased risk was observed for those who carried 5-8 risk genotypes (adjusted OR = 1.04; 95% CI = 0.86-1.26) and 9-10 risk genotypes (adjusted OR = 1.62; 95% CI = 1.14-2.30) in a dose-response manner (P = 0.045). Furthermore, the joint effect was more pronounced among patients with oropharyngeal cancer, younger adults (≤57 yr old), men, non-smokers, non-drinkers, and individuals with family history of cancer in first-degree relatives. Additionally, we also observed that those with 5-10 risk genotypes had an earlier SCCHN onset than those with 0-4 risk genotypes, particularly for non-smokers and/or non-drinkers. We concluded that E2F1 and E2F2 genetic variants may jointly play important roles in head and neck carcinogenesis.

Background NBS1 is a key DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint that plays important roles in maintaining genomic stability. The NBS1 8360G>C (Glu185Gln) is one of the most commonly studied polymorphisms of the gene for their association with risk of cancers, but the results are conflicting. Methods We performed a meta-analysis using 16 eligible case-control studies (including 17 data sets) with a total of 9,734 patients and 10,325 controls to summarize the data on the association between the NBS1 8360G>C (E185Q) polymorphism and cancer risk. Results Compared with the common 8360GG genotype, the carriers of variant genotypes (i.e., 8360 GC/CC) had a 1.06-fold elevated risk of cancer (95% CI = 1.00–1.12, P = 0.05) in a dominant genetic model as estimated in a fixed effect model. However, the association was not found in an additive genetic model (CC vs GG) (odds ratio, OR = 0.98, 95% CI = 0.85–1.13, P = 0.78) nor in a recessive genetic model (CC vs GC +GG) (OR = 0.94, 95% CI = 0.82–1.07, P = 0.36). The effect of the 8360G>C (E185Q) polymorphism was further evaluated in stratification analysis. It was demonstrated that the increased risk of cancer associated with 8360G>C variant genotypes was more pronounced in the Caucasians (OR = 1.07, 95% CI = 1.01–1.14, P = 0.03). Conclusion Our meta-analysis suggests that the NBS1 E185Q variant genotypes (8360 GC/CC) might be associated with an increased risk of cancer, especially in Caucasians.