Identification and validation of novel lung adenocarcinoma subtypes and construction of prognostic models: based on cuprotosis-related genes.

Cuprotosis is a novel and unique form of cell death that is of great value in a variety of cancers. However, the prognostic role of cuprotosis-related genes (CRGs) in lung cancer remains undetermined. We compared the expression profile of CRGs in lung adenocarcinoma (LUAD) patients, revealing the genetic alterations and inter-gene correlations of CRGs. Based on 13 CRGs, LUAD patients could be well differentiated into two molecular subgroups, and the differentially expressed genes (DEGs) in these molecular subtypes were identified. Furthermore, 10 cuprotosis pattern-related DEGs with a significant prognostic value were obtained for constructing a prognostic model. Through validation in an external validation set, the prognostic model based on the CRGs-risk score showed the robust and effective predictive ability and served as an independent prognostic indicator for LUAD patients. Therefore, combining the CRGs-risk score with multiple factors such as clinicopathological characteristics, a quantitative nomogram was developed to predict the survival and prognosis of LUAD patients, improving the clinical application value of the CRGs-risk score. In the low CRGs-risk score group, the related immune cell infiltration was increased and the immune function was activated in LUAD patients. This study may add to the knowledge of CRGs in LUAD, partly contribute to evaluating the prognosis of LUAD patients, and provide direction for the development of targeted therapy and immunotherapy.

m7G-Associated subtypes, tumor microenvironment, and validation of prognostic signature in lung adenocarcinoma.

Background: 7-Methylguanosine (m7G) is an important posttranscriptional modification that regulates gene expression and is involved in tumorigenesis and development. Tumor microenvironment has been proven to be highly involved in tumor progression and prognosis. However, how m7G-associated genes affect the tumor microenvironment of patients with lung adenocarcinoma (LUAD) remains to be further clarified. Methods: The genetic alterations of m7G-associated genes and their associations with the prognosis and tumor microenvironment in LUAD patients were systemically analyzed. An m7G-Riskscore was established and analyzed for its performance in disease prognosis and association with patient response to immunotherapy. Expression of the model genes at the protein level was investigated through ex vivo experiments. A nomogram was finally obtained based on the m7G-Riskscore and several significant clinical pathological features. Results: m7G-Associated genes were obtained from five LUAD datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases, and their expression pattern was determined. Based on the m7G-associated genes, three LUAD clusters were defined. The differentially expressed genes from the three clusters were screened and used to further divide the LUAD patients into two gene clusters. It was demonstrated that the alterations of m7G-associated genes were associated with the clinical pathological features, prognosis, and tumor immune infiltration in LUAD patients. An m7G-Riskscore including CAND1, RRM2, and SLC2A1 was obtained with robust and accurate prognostic performance. WB and cell immunofluorescence also showed significant dysregulation of CAND1, RRM2, and SLC2A1 in LUAD. In addition, a nomogram was established to improve the clinical feasibility of the m7G-Riskscore. Correlation analysis revealed that patients with a lower m7G-Riskscore had higher immune and stromal scores, responded well to chemotherapeutics and multiple targeted drugs, and survived longer. Patients with a higher m7G-Riskscore tended to suffer from a higher tumor mutation burden. Furthermore, the m7G-Riskscore exhibited significant associations with immune cell infiltration and cancer stemness. Conclusion: This study systemically analyzed m7G-associated genes and identified their potential role in tumor microenvironment and prognosis in patients with LUAD. The findings of the present study may help better understand LUAD from the m7G perspective and also provide a new thought toward the prognosis and treatment of LUAD.

A Novel Prognostic Model Based on Seven Necroptosis-Related miRNAs for Predicting the Overall Survival of Patients with Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) remains one of the leading causes of cancer-related deaths worldwide. This study is aimed at constructing a risk scoring model based on necroptosis-related miRNAs to predict prognosis of LUAD. Expression profile of miRNA in LUAD was downloaded from The Cancer Genome Atlas (TCGA) database. We screened the differentially expressed necroptosis-related miRNAs between LUAD patients and normal samples, thus constructed a seven miRNA-based risk stratification on the basis of the TGCA cohort. This risk stratification was prove to be effective in predicting the overall survival (OS) of patients with LUAD. Furthermore, we constructed a nomogram model based on the combination of risk characteristics and clinicopathological features, which was also prove to be accurate and efficient in predicting OS of LUAD patients. Functional enrichment analyses on the targeted genes of these miRNAs with prognostic value were carried out. Results indicated that these targeted genes were closely related to the development and metastasis of tumors. In summary, our research has developed a prognostic model based on the expression of miRNAs related to necroptosis. This model might be used to predict the prognosis of LUAD accurately, which might be helpful in improving treatment efficacy of LUAD.

Prognostic value of EGFR and p-EGFR in nasopharyngeal carcinoma: A systematic review and meta-analysis.

PURPOSE: To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma. METHODS: A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). RESULTS: A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I2 = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I2 = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12). CONCLUSION: In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker. ETHICS AND DISSEMINATION: This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications. INPLASY REGISTRATION NUMBER: INPLASY 202150010.

Detection of Chlamydia psittaci and Chlamydia ibidis in the Endangered Crested Ibis (Nipponia nippon).

Chlamydia spp. are a group of obligate intracellular pathogens causing a number of diseases in animals and humans. Avian chlamydiosis (AC), caused by Chlamydia psittaci (C. psittaci) as well as new emerging C. avium, C. gallinacea and C. ibidis, have been described in nearly 500 avian species worldwidely. The Crested Ibis (Nipponia nippon) is a world endangered avian species with limited population and vulnerable for various infections. To get a better understanding of the prevalence of Chlamydia spp. in the endangered Crested Ibis, faecal samples were collected and analysed. The results confirmed that 20.20% (20/99) of the faecal samples were positive for Chlamydiaceae and were identified as C. ibidis with co-existence of C. psittaci in one of the 20 positive samples. In addition, ompA sequence of C. psittaci obtained in this study was classified into the provisional genotype Matt116, while that of C. ibidis showed high genetic diversity, sharing only 77% identity with C. ibidis reference strain 10-1398/6. We report for the first time the presence of C. ibidis and C. psittaci in the Crested Ibis, which may indicate a potential threat to the endangered birds and should be aware of the future protection practice.

Modified Yupingfeng formula for the treatment of stable chronic obstructive pulmonary disease: a systematic review of randomized controlled trials.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), is a very common disease of respiratory system. An increasing number of clinical trials on Yupingfeng formula in the management of stable COPD have been performed. However, the evidence base for it remains unknown. This review aims at assessing the efficacy, and safety of modified Yupingfeng formula in the treatment of stable COPD through a systematic review of all available randomized controlled trials. MATERIALS AND METHODS: Literature retrieval was conducted using four English databases (CENTRAL, PubMed, EMBASE, and ISI Web of Science), and four Chinese databases (CBM, CNKI, VIP, and WANFANG), from respective inception to January 2013, and supplemented with a manual search. Review authors independently extracted the trial data, and assessed the quality of each trial. Methodological quality was assessed by Cochrane risk of bias and Jadad's scale. The following outcomes were evaluated: (1) lung function; (2) 6-minute walk distance (6MWD); (3) effective rate; (4) serum levels of IgA, IgG and IgE; and (5) adverse events. Data were analyzed using STATA 12.0 software. RESULTS: A total of nine studies involving 660, stable COPD patients were identified. Patients from all studies included in this review were randomized to receive Yupingfeng formula combined with Western medications in comparison with Western medications. In general, the methodological quality of the included trials was poor. The results of this systematic review indicates that, compared with Western medications alone, the use of Yupingfeng formula, if combined with Western medications could significantly improve FEV1 (WMD = 0.30L; 95%CI: 0.19, 0.42), FEV1/FVC ratio (SMD = 0.69; 95%CI: 0.48, 0.91), 6MWD (WMD = 31.73m; 95% CI: 19.29, 44.17), and effective rate (RR = 1.24; 95% CI: 1.10, 1.41), and increase the serum levels of IgA (WMD = 0.25; 95%CI: 0.16, 0.34) and IgG (WMD = 1.10; 95%CI: 0.53, 1.68), but no difference was found in the serum IgE levels (WMD = 0.47; 95%CI: -0.32, 1.27) between the two groups. No serious adverse events were reported. CONCLUSIONS: Within the limitations of this systematic review, we may conclude that compared with Western medications alone, Yupingfeng formula, when combined with Western medications can provide more benefits for patients with stable COPD, without any serious adverse reactions being identified. However, these benefits need to be further confirmed through high-quality prospective placebo-controlled trials that should be strictly conducted in accordance with methodological principles and procedures.