Meixia Lu

As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNA dysfunction and even cancer. Nevertheless, studies on the association between lncRNA‐associated single‐nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22–1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95% CI: 1.15–1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA‐616‐3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR‐616‐3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.

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 (P_trend < 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 < .001) and Cancer Cohort (16% and 2%, both P < 0.001). The 12‐month all‐cause post‐discharge mortality rate in survival discharged Cancer COVID‐19 Cohort (8%) was higher than that in COVID‐19 Cohort (0.4%, P < .001) but similar to that in Cancer Cohort (15%, P = .084). The incidence of sequelae in Cancer COVID‐19 Cohort (23%, 26/114) is similar to that in COVID‐19 Cohort (30%, 130/432, P = .13). The 1‐year all‐cause mortality was high among patients with hematologic malignancies (59%), followed by those who have nasopharyngeal, brain, and skin tumors (45%), digestive system neoplasm (43%), and lung cancers (32%). The rate was moderate among patients with genitourinary (14%), female genital (13%), breast (11%), and thyroid tumors (0). COVID‐19 patients with cancer showed a high rate of in‐hospital mortality and 1‐year all‐cause mortality, but the 12‐month all‐cause post‐discharge mortality rate in survival discharged cancer COVID‐19 patients was similar to that in Cancer Cohort. Comparing to COVID‐19 Cohort, risk stratification showed that hematologic, nasopharyngeal, brain, digestive system, and lung tumors were high risk (44% vs 9%, P < 0.001), while genitourinary, female genital, breast, and thyroid tumors had moderate risk (10% vs 9%, P = .85) in COVID‐19 Cancer Cohort. Different tumor subtypes had different effects on COVID‐19. But if cancer patients with COVID‐19 manage to survive their COVID‐19 infections, then long‐term mortality appears to be similar to the cancer patients without COVID‐19, and their long‐term clinical sequelae were similar to the COVID‐19 patients without cancer.

Myopia is the leading cause of visual impairments worldwide. Some studies revealed that visual experience in early life affected the final myopia, indicating that environmental factors play an impellent role in the development of myopia. However, risk factors of myopia are still not identified among adolescents in China. A total of 4104 cases of myopia symptom and 3306 emmetropia controls were selected from students in primary and middle schools in Wuhan in 2008. We identified the risk factors associated with myopia symptom by multivariate logistic regression in this cross-sectional study and constructed a risk score system for myopia symptom. The value of the area under the receiver operating characteristic curve (ROC) was 0.735. Furthermore, we followed up 93 students aged 7–9 years for one year and calculated the total points using the score system. We found no significant difference between the final myopia symptom and the results predicted by the total points by pair chi-square test (P>0.05). The score system had a modest ability to estimate the risk factors of myopia symptom. Using this score system, we could identify the students who are at risk of myopia symptom in the future according to their behaviors and environmental factors, and take measures to slow the progress of myopia symptom.

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.

MicroRNA signatures predict prognosis of patients with glioblastoma multiforme through the cancer genome atlas

To re-evaluate the efficacy of Meniett therapy for the treatment of Ménière's disease (MD). PubMed, Embase, Cochrane Library, Clinicaltrials.gov, ChiCTR, and the CNKI database were searched for articles in English and Chinese published before August 31, 2015. Included in this meta-analysis were studies that dealt with outcomes of Meniett therapy for the treatment of MD, including randomized controlled clinical trials, case-control studies, and prospective or retrospective cohort studies, with sample sizes of ≥ 10 subjects. Keywords included endolymphatic hydrops, Ménière's disease, pressure, Meniett, and transtympanic micropressure treatment. Fourteen studies were included, involving a total of 345 MD patients. Data were analyzed using the Meta package in R. Dichotomous outcomes were expressed as risk ratios with 95% confidence intervals, and weighted mean differences with 95% confidence intervals were used to present continuous outcomes. Heterogeneity of the included studies was quantitatively assessed by χ(2) and I tests. Fixed-effects models were used for I(2) <50%; otherwise, random-effects models were used. Funnel plots were constructed to test the publication bias. This study showed that Meniett therapy may prevent vertigo attacks and substantially reduce its frequency in MD patients. It may also alleviate the functional deficit. The impact of Meniett therapy on hearing remains uncertain. The optimal effect might maintain for approximately 18 months. This meta-analysis suggested that Meniett therapy may be a useful second-line therapy in the treatment of MD.

Identification of a six microRNA signature as a novel potential prognostic biomarker in patients with head and neck squamous cell carcinoma

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.

The p16^INK4a 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 P^16INK4a promoter between cancer and the corresponding control group. Therefore, we conducted a meta-analysis to better identify the association. PubMed, Ovid, ISI Web of Science, and EMBASE were searched to identify eligible studies to evaluate the association of p16^INK4a promoter methylation and HNSCC. Odds ratio (ORs) and 95% confidence intervals (95%CI) were calculated to evaluate the strength of association between p16^INK4a promoter methylation and HNSCC. A total of twenty-one studies with 1155 cases and 1017 controls were included in the meta-analysis. The frequencies of p16^INK4a 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. This meta-analysis of 21 published studies identified that aberrant methylation of p16^INK4a promoter was found to be significantly associated with HNSCC.