The predictive value of E2F7 in immunotherapy efficacy for lung adenocarcinoma: An observational study.

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. In recent years, immunotherapy has greatly changed the treatment pattern of advanced LUAD. However, only a small proportion of LUAD patients benefitted from immune checkpoint inhibitor therapy. There is an urgent need to develop a biomarker to predict immune therapy response. E2F7 has been shown to be closely related to immune cell infiltration and immune checkpoint expression in tumors. However, it is unclear whether the E2F7 expression is related to the immunotherapy efficacy in LUAD. Therefore, we conducted this study to investigate the clinical characteristics, function, and immunotherapy responsiveness of E2F7 expression, and to explore the potential of E2F7 as an immunotherapy response biomarker in LUAD. We analyzed the clinical characteristics and biological function of E2F7 expression based on data from the Cancer Genome Atlas and Gene Expression Omnibus database. In addition, we used single-cell sequencing data to analyze the immune regulatory effects of E2F7 in LUAD. Furthermore, we analyzed the immunotherapy response prediction ability of E2F7 expression based on the immunotherapy database. Compared to normal lung tissue, E2F7 was specifically overexpressed in LUAD, and its expression was associated with higher malignancy and poor efficacy. E2F7 high expression was an independent risk factor affecting the prognosis of LUAD. E2F7 was enriched in cell division and cell cycle functions. In addition, the expressions of immune checkpoints were correlated with the E2F7 expression. E2F7 was highly expressed in myeloid cells, and E2F7 highly expressed myeloid cells were associated with immune and inflammatory responses. Moreover, the expression level of E2F7 can effectively distinguish different immune therapy responses in LUAD patients. E2F7 was upregulated in LUAD, and high expression of E2F7 was associated with higher malignancy and poor efficacy. E2F7 high expression was an independent risk factor affecting the prognosis of LUAD. Moreover, E2F7 may exert its immunosuppressive effect by affecting the function of myeloid cells. These results indicated the potential role of E2F7 as a biomarker for predicting LUAD immunotherapy responses.

MiR-204-5p-targeted AP1S2 is necessary for papillary thyroid carcinoma.

MiR-204-5p, as a tumour suppressor, has been found in several cancers. However, whether miR-204-5p is involved in papillary thyroid carcinoma (PTC) has not yet been investigated. In this study, we identified miR-204-5p as a down-regulated miRNA in PTC tissues, unveiling that the levels of miR-204-5p in serum of patients with PTC were linked to PTC risk, and that the expression in patients concomitant with both PTC and benign lesions was much lower than that in patients only with PTC. Furthermore, we documented that miR-204-5p inhibited proliferation, migration, invasion, and cell cycle progression and triggered apoptosis of PTC cells via cell biology experiments. Finally, we identified that AP1S2 was a target of miR-204-5p using RNA-seq, iTRAQ, and bioinformatics prediction. Overall, miR-204-5p functions as a suppressor for PTC pathogenesis via the miR-204-5p/AP1S2 axis.

Colony­stimulating factor CSF2 mediates the phenotypic plasticity of small­cell lung cancer by regulating the p­STAT3/MYC pathway.

Relapse and drug resistance are the main causes of mortality in patients with small­cell lung cancer (SCLC). Intratumoral heterogeneity (ITH) is a key biological mechanism that leads to relapse and drug resistance. Phenotypic plasticity is an important factor that leads to ITH in SCLC, although its mechanisms and key regulatory factors remain to be elucidated. In the present study, cell proliferation and cell switch assay were measured using trypan blue. Alamar Blue was used to test drug sensitivity. Differential genes were screened by RNA sequencing. Reverse transcription­quantitative PCR and western blotting were performed to assess the expressions of CSF2/p­STAT3/MYC pathway related molecules, neuroendocrine (NE)/non­neuroendocrine (non­NE), transcription factors and drug­related targets. The present study found that SCLC cell line NCI­H69 exhibited adherent (H69A) and suspensive (H69S) phenotypes, which could switch back and forth. The two phenotypic cells had significant differences in cellular NE and non­NE characteristics, drug sensitivity and expression of drug­related targets. RNA sequencing showed that granulocyte­macrophage colony­stimulating factor [i.e., colony­stimulating factor 2 (CSF2)] was the main differentially expressed gene between the two phenotypes and that H69A cells highly expressed CSF2. The inhibition of CSF2 promoted the transformation from H69A to H69S, increased drug sensitivity and NE marker expression and decreased the non­NE marker expression in H69A. The STRING, Pathway Commons and Reactome databases showed a potential regulatory relationship between CSF2 and phosphorylated signal transducer and activator of transcription 3 (p­STAT3)/MYC. p­STAT3 and MYC expression was higher in H69A cells than in H69S cells and CSF2 silencing inhibited their expression. Taken together, these results indicated that CSF2 may regulate the phenotypic plasticity of SCLC through the phosphorylated STAT3/MYC pathway, thereby limiting the transformation between cell clones with different phenotypes and changing the sensitivity of specific cell clones to targeted drugs. Targeting CSF2 may be a potential therapeutic strategy to overcome drug resistance in SCLC treatment by influencing ITH.

ε2 allele and ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) may confer the association of APOE genetic polymorphism with risks of nephropathy in type 2 diabetes: a meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) contributes to end-stage renal failure. Microvascular injury resulted from reactive oxygen species is implicated in the pathogenesis of DN. Genetic polymorphism of Apolipoprotein E (APOE) influences the antioxidative properties of the protein. The relationship of APOE polymorphism with the risks of nephropathy in type 2 diabetes (T2DN) remains elusive. METHODS: An up-to-date meta-analysis was conducted on the basis of studies selected from PubMed, WanFang database, Embase, Vip database, Web of Science, Scopus, and CNKI database. RESULTS: A total of 33 studies conferring 3266 cases and 3259 controls were selected on the basis of criteria of inclusion and exclusion in this meta-analysis. For APOE alleles, the pooled odds ratio (OR) of ε2 vs. ε3 was 1.89 (95% confidence intervals [95% CI]: 1.49-2.38, P < 0.0001). With regard to APOE genotypes, ε2/ε2, ε2/ε3, and ε2/ε4 increased the risk of T2DN (ε2/ε2 vs. ε3/ε3: OR = 2.32, 95% CI: 1.52-3.56, P = 0.0001; ε2/ε3 vs. ε3/ε3: OR = 1.97, 95% CI: 1.50-2.59, P<0.0001; ε2/ε4 vs. ε3/ε3: OR = 1.69, 95% CI: 1.18-2.44, P = 0.0046). CONCLUSIONS: This meta-analysis found that the APOE ε2 allele and the ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) are the risk factors of T2DN.

Association of rs944289, rs965513, and rs1443434 in TITF1/TITF2 with Risks of Papillary Thyroid Carcinoma and with Nodular Goiter in Northern Chinese Han Populations.

OBJECTIVE: In this study, we aimed to investigate the associations of three single-nucleotide polymorphisms (SNPs) on TITF1/TITF2 (rs944289, rs965513, and rs1443434) with susceptibility to papillary thyroid carcinoma (PTC) and with nodular goiter (NG) in northern Chinese Han populations. METHODS: We performed a case-control study comprising 861 PTC patients, 562 NG patients, and 896 normal controls (NCs). One TITF1 SNP (rs944289) and two TITF2 SNPs (rs965513 and rs1443434) were genotyped. Departures from Hardy-Weinberg equilibrium (HWE) in the control group were evaluated using chi-square test. Associations of the SNPs with PTC and with NG were assessed by unconditional logistic regression using the online SNPStats program. Bonferroni correction was performed for multiple tests in genotype analyses. Data analysis was performed by SPSS24.0 unless otherwise specified. RESULTS: For rs944289, T allele was associated with increased risks for both PTC (OR = 1.23, 95% CI: 1.08-1.41, P=0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, P=0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, P=0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, P=0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, P=0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, P=0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, P=0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50, P=0.002) and NG (OR = 1.28, 95% CI: 1.10-1.50. CONCLUSIONS: There are associations of rs944289 and rs1443434 polymorphisms with PTC risk and association of rs944289 polymorphism with NG risk. Haplotypes T-G-G and T-G-T are risk haplotypes of PTC and NG, respectively.

Prevalence of autism spectrum disorder in Asia: A systematic review and meta-analysis.

There has been an increased prevalence of the diagnosis of Autism Spectrum Disorder (ASD) globally during the last decade. An updated and overall estimate of ASD prevalence in Asia would assist health professionals to develop relevant public health strategies. We performed a systematic review by searching English databases (Medline, Embase, Web of Science, and Cochran Library) from inception date to August 6, 2018. Subgroup, sensitivity, and meta-regression analyses were performed to address heterogeneity. Publication bias was evaluated using Egger's test. A total of 2,195,497 subjects in Asia from 12 eligible studies were included in this meta-analysis. The pooled estimate of ASD prevalence among the included subjects was 0.36% (95% CI: 0.16-0.79%). The pooled ASD prevalence in males (0.45%, 95% CI: 0.19-1.04%) was higher than that in females (0.18%, 95% CI: 0.079-0.49%). ASD prevalence in East Asia, South Asia, and West Asia was 0.51% (95% CI: 0.06-4.22%), 0.31% (95% CI: 0.14-0.65%), and 0.35% (95% CI: 0.07-1.80%) respectively. The prevalence of ASD is increasing in Asia. Universal and standardized diagnostic processes for ASD should be adopted for the prevention and control programs of ASD in future.

SHANK1 polymorphisms and SNP-SNP interactions among SHANK family: A possible cue for recognition to autism spectrum disorder in infant age.

Autism spectrum disorder (ASD) is a serious lifelong neurodevelopmental disorder. ASD is diagnosed for children at the age of two. ASD diagnosis, as early as possible, lays the foundation for treatment and much better prognosis. Notably, gene-based test is an inherent method to recognize the potential infants with ASD before the age of two. To investigate whether SHANK family contributes to ASD prediction, on the basis of our previous studies of SHANK2 and SHANK3, we further investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. We enrolled 470 subjects (229 cases and 241 healthy controls) who were northeast Chinese Han. Four tag SNPs (rs73042561, rs3745521, rs4801846, and rs12461427) of SHANK1 were selected and genotyped. We used the SNPStats online analysis program to assess the associations between the four SNPs and ASD risk. The SNP-SNP interactions among SHANK family were analyzed using multifactor dimensionality reduction method. We found that the four SHANK1 SNPs were not associated with ASD risk in northeast Chinese Han population. There existed a strong synergistic interaction between rs11236697 [SHANK2] and rs74336682 [SHANK2], and moderate synergistic interactions (rs74336682 [SHANK2]-rs73042561 [SHANK1], rs11236697 [SHANK2]-rs77716438 [SHANK2], and rs11236697 [SHANK2]-rs75357229 [SHANK2]). These SHANK1 variants may not affect the susceptibility to ASD in Chinese Han population. SNP-SNP interactions in SHANK family may confer ASD risk. Autism Res 2019, 12: 375-383 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is a serious lifelong neurodevelopmental disorder with strong genetic components. We investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. Our results indicated that there exists no association between SHANK1 SNPs and ASD, and SNP-SNP interactions in SHANK family may confer ASD risk in the Northeast Han Chinese population. Future studies are needed to test more SHANK family SNPs in a large sample to demonstrate the associations.

Association between ApoE polymorphism and hypertension: A meta-analysis of 28 studies including 5898 cases and 7518 controls.

Hypertension is one of the most common chronic diseases, constituting an independent risk factor for many diseases. Our study aimed to evaluate the association between apolipoprotein E (ApoE) genetic polymorphism and hypertension, and to provide evidence for the etiology of hypertension. Case-control studies of ApoE polymorphism and hypertension, which were included in PubMed, Embase, Web of Science, Medline, WanFang, Vip, and CNKI information databases, were selected and evaluated according to criteria of inclusion and exclusion. Eligible data were extracted and pooled, and were analyzed and assessed using Stata 12.0. Random-effect models were used when heterogeneity existed in between-study, and fixed-effect models were applied otherwise. A total of 28 studies that consisted of 5898 cases with hypertension and 7518 controls were selected. Alleles and genotypes of ApoE between cases and controls were compared. For ApoE alleles, we observed the contrast of ApoE ε2 versus ε3 allele yielded a pooled OR of 0.99 (95% CI: 0.87-1.11; P = 0.823), whereas the contrast of ε4 versus ε3 allele yielded a pooled OR of 1.95 (95% CI: 1.50-2.54; P < 0.001). For ApoE genotypes, compared with ε3/ε3 genotype, genotypes (ε2/ε2 and ε2/ε3) showed a possible association with hypertension (OR = 0.88; 95% CI: 0.79-0.99; P = 0.033), and genotypes (ε3/ε4 and ε4/ε4) had a 2.08-fold risk of developing hypertension (OR = 2.08; 95% CI: 1.58-2.74; P < 0.001). There is the association between ApoE polymorphism and hypertension: the genotypes carrying ε2 allele may be a protective factor, and the ApoE ε4 allele and the genotypes carrying ε4 allele may be risk factors for hypertension.