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BACKGROUND: Non-small-cell lung cancer (NSCLC) is a common cancer. Chemotherapeutic drug resistance limits the therapeutic effect of NSCLC and leads to a poor prognosis. As a result, new specific targets may be better identified by studying the mechanism of drug resistance to cisplatin in NSCLC. METHODS: In the present study, we performed a quantitative real-time polymerase chain reaction and western blotting to detect mRNA and protein levels. The proliferation of cells was analyzed by a Cell Counting Kit-8 and colony formation assays. Cell invasion was measured via the Transwell assay. A scratch assay was performed to measure cell migration in cisplatin (DDP)-resistant NSCLC cells. Apoptosis of cells was examined using flow cytometry. RESULTS: We found that circANKRD28 was notably decreased in NSCLC. The results showed that circANKRD28 expression was not affected, and its half-life was more than 12 h. Functional experiments revealed that circANKRD28 overexpression inhibited DDP resistance in NSCLC cells in vitro. Mechanistic findings demonstrated that circANKRD28 regulated tumor cell progression and DDP sensitivity through the miR-221-3p/SOCS3 axis. CONCLUSIONS: The present study revealed the regulatory effects and molecular mechanism of circANKRD28 on the development and cisplatin resistance in NSCLC, which may provide experimental basis and theoretical support to identify new targets for therapy of DDP resistance in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , RNA Circular/genéticaRESUMO
OBJECTIVE: This study aimed to investigate the longitudinal circulating eosinophil (EOS) data impacted by the COVID-19 vaccine, the predictive role of circulating EOS in the disease severity, and its association with T cell immunity in patients with SARS-CoV-2 Omicron BA.2 variant infection in Shanghai, China. METHODS: We collected a cohort of 1,157 patients infected with SARS-CoV-2 Omicron/BA.2 variant in Shanghai, China. These patients were diagnosed or admitted between Feb 20, 2022, and May 10, 2022, and were classified as asymptomatic (n = 705), mild (n = 286) and severe (n = 166) groups. We compiled and analyzed data of patients' clinical demographic characteristics, laboratory findings, and clinical outcomes. RESULTS: COVID-19 vaccine reduced the incidence of severe cases. Severe patients were shown to have declined peripheral blood EOS. Both the 2 doses and 3 doses of inactivated COVID-19 vaccines promoted the circulating EOS levels. In particular, the 3rd booster shot of inactivated COVID-19 vaccine was shown to have a sustained promoting effect on circulating EOS. Univariate analysis showed that there was a significant difference in age, underlying comorbidities, EOS, lymphocytes, CRP, CD4, and CD8 T cell counts between the mild and the severe patients. Multivariate logistic regression analysis and ROC curve analysis indicate that circulating EOS (AUC = 0.828, p = 0.025), the combination of EOS and CD4 T cell (AUC = 0.920, p = 0.017) can predict the risk of disease severity in patients with SARS-CoV-2 Omicron BA.2 variant infection. CONCLUSIONS: COVID-19 vaccine promotes circulating EOS and reduces the risk of severe illness, and particularly the 3rd booster dose of COVID-19 vaccine sustainedly promotes EOS. Circulating EOS, along with T cell immunity, may have a predictive value for the disease severity in SARS-CoV-2 Omicron infected patients.
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Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , China/epidemiologia , Eosinófilos , SARS-CoV-2 , Gravidade do PacienteRESUMO
Long non-coding RNA brain cytoplasmic RNA 1 (LncRNA BCYRN1) has been proved to participate in the cancer cell metastasis process, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms involved in the BCYRN1-mediated function remain largely unknown. The qRT-PCR analysis was carried out to examine the relative expressions of BCYRN1, microRNA-30b-3p (miR-30b-3p), and Rho-associated coiled-coil protein kinase 1 (ROCK1). ROCK1 protein level was detected via western blot assay. The migrative and invasive abilities of H520 and A549 cells were evaluated via Transwell assay. The relationships between BCYRN1 and miR-30b-3p or ROCK1 and miR-30b-3p were examined by luciferase reporter assay. The expression levels of BCYRN1 and ROCK1 were upregulated in NSCLC tissues and cells, while miR-30b-3p was downregulated. Higher BCYRN1 expression indicated lymph node metastasis and advanced tumor-node-metastasis (TNM) stage of NSCLC patients. Loss of BCYRN1 suppressed cell migration and invasion. More importantly, miR-30b-3p possessed the binding sites with BCYRN1. Besides, BCYRN1 negatively regulated the expression level of miR-30b-3p. Meanwhile, ROCK1 was proven to be directly targeted by miR-30b-3p. In addition, the silencing of miR-30b-3p also weakened the effect of BCYRN1 knockdown on cell migration and invasion. In vivo, BCYRN1 silencing reduced the growth of A549 cells. LncRNA BCYRN1 was involved in the metastasis of NSCLC through modulating the miR-30b-3p/ROCK1 axis.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Encéfalo/metabolismo , Encéfalo/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismoRESUMO
To investigate the distribution and risk factors of pathogens in secondary pulmonary infection in patients with COVID-19.142 patients with confirmed COVID-19 from Shanghai Public Health Clinical Center were collected, and 32 patients with pulmonary infection were taken as the infection group. The distribution of pathogens in the sputum specimens was applied for retrospective analysis. Meanwhile, 110 patients diagnosed with COVID-19, but without pulmonary infection were regarded as the asymptomatic group. The risk factors of pulmonary infection were analyzed with generalized linear models and logistic regression. The pathogens in the lung infection group were mainly gram-negative bacteria (22, 68.8%), especially Klebsiella pneumoniae. Gram-positive bacteria and fungi accounted for 13 (40.6%), mainly Staphylococcus aureus, and 11 (34.4%), mainly Candida albicans. There were 14 cases (43.8%) infected with two or more pathogens. The comparison between the two groups found that, patients with elder age, underlying diseases, more lung lesions and low protein contents, were more likely to develop lung infections. At last, univariate analysis showed that 6 factors, including indwelling gastric catheter, the number of deep vein catheters, tracheal intubation tracheotomy, invasive mechanical ventilation, hormonal application, and the use of more than three antibacterial drugs, are risk factors for COVID-19 secondary pulmonary infection. Generalized linear models and logistic regression analysis showed antimicrobial use as an independent risk factor for COVID-19 secondary lung infection. There are many risk factors for secondary lung infection in severe COVID-19 patients, and it is recommended to use antibiotics reasonably.
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COVID-19 , Idoso , China/epidemiologia , Humanos , Pulmão , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
Lung cancer is regarded as one of the dominant causes in cancer patients among men and women all over the world. Rho-associated coiled-coil forming protein kinase l (ROCK1) is characterized as pivotal downstream effectors of the small GTPase RhoA and reported to participate in tumor metastasis. miR-335-5p acts as tumor suppressor microRNA and is identified to be downregulated in tumor tissues. miR-335-5p/ROCK1 axis has been demonstrated to promote cell proliferation and metastasis in gastric cancer, hepatocellular carcinoma and so on. However, the role it plays in promoting cell proliferation in non-small cell lung cancer (NSCLC) is poorly understood. Here, we demonstrated that the upregulated expression of ROCK1 was highly correlated with downregulated expression of miR-335-5p in NSCLC tissues and cell lines. Mechanistically, Knockdown of ROCK1 inhibited cell proliferation in vitro, accompanied by cell cycle change confirmed by flow analysis. Furthermore, miR-335-5p can downregulate the ROCK1 expression by directly binding to the 3'-untranslated region in posttranscriptional level. In vivo animal model showed similar results. Our findings highlighted the crucial role that miR-335-5p acted as a tumor suppressor to modulate cell proliferation and cell cycle progression via downregulating ROCK1 expression. And this miR-335-5p/ROCK1 axis contributed to NSCLC pathogenesis and might be promising targets for NSCLC therapy.
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Neuropilin 1 (NRP1) is a transmembrane glycoprotein that acts as a co-receptor for multiple extracellular ligands and typically performs growth-promoting functions in cancer cells. Accumulating evidence indicates that NRP1 is upregulated, and may be an independent predictor of cancer relapse and poor survival, in many cancer types, including non-small cell lung cancer (NSCLC). Recent evidence suggests that NRP1 affects tumour cell viability via the epidermal growth factor receptor (EGFR) and Erb-B2 receptor tyrosine kinase 2 (ErbB2) signalling pathways in venous endothelial cells and in multiple cancer cells. In the present study, we aimed to evaluate the role of NRP1 in NSCLC tumourigenesis and to explore a new post-transcriptional mechanism of NRP1 regulation via a microRNA that mediates EGFR signalling regulation in lung carcinogenesis. The results showed that miR-338-3p is poorly expressed and NRP1 is overexpressed in NSCLC tissues relative to their levels in adjacent noncancerous tissues. Luciferase reporter assays, quantitative real-time reverse transcription PCR, and Western blot analyses showed that NRP1 is a direct target of miR-338-3p. Overexpression of miR-338-3p in NSCLC cell lines inhibited cell proliferation in vitro and in vivo. Moreover, cell migration and invasion were inhibited by miR-338-3p overexpression. These effects occurred via the EGF signalling pathway. Our data revealed a new post-transcriptional mechanism by which miR-338-3p directly targets NRP1; this mechanism plays a role in enhancing drug sensitivity in EGFR wild-type patients with NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Neuropilina-1/genética , Regiões 3' não Traduzidas , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Camundongos , Transplante de Neoplasias , Prognóstico , Transdução de Sinais , Análise de Sobrevida , Regulação para CimaRESUMO
BACKGROUND: Significant evidence has shown that the miRNA pathway is an important component in the downstream signaling cascades of TGF-ß1 pathway. Our previous study has indicated that miR-335-5p expression was significantly down-regulated and acted as a vital player in the metastasis of non-small cell lung cancer (NSCLC), however the underlying mechanism remained unclear. METHODS: The differential expression level of miR-335-5p and ROCK1 were determined by qRT-PCR and IHC analysis in human tissue samples with or without lymph node metastasis. Transwell assay was conducted to determine cell ability of migration and invasion. SiRNA interference, microRNA transfection and western blot analysis were utilized to clarify the underlying regulatory mechanism. RESULTS: We showed that down-regulated expression of miR-335-5p and up-regulated expression of ROCK1 in NSCLC tissues were associated with lymph node metastasis. Over-expresion of miR-335-5p significantly inhibited TGF-ß1-mediated NSCLC migration and invasion. Furthermore, luciferase reporter assays proved that miR-335-5p can bind to 3'-UTR of ROCK1 directly. Moreover, we confirmed that siRNA-mediated silencing of ROCK1 significantly diminished TGF-ß1-mediated EMT and migratory and invasive capabilities of A549 and SPC-A1 cells. CONCLUSION: This is the first time to report that miR-335-5p regulates ROCK1 and impairs its functions, thereby playing a key role in TGF-ß1-induced EMT and cell migration and invasion in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Pulmonares/metabolismo , MicroRNAs/biossíntese , Fator de Crescimento Transformador beta1/farmacologia , Quinases Associadas a rho/biossíntese , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/genética , Quinases Associadas a rho/genéticaRESUMO
OBJECTIVES: Lung cancer is an independent risk factor for pulmonary complications following HIV infection. This study aimed to examine the expression and clinical significance of Cathepsin G (CTSG) protein in both non-HIV and HIV-related lung cancers. METHODS: The data related to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) in the TCGA dataset and the data related to healthy individuals in the GTEx dataset, the GEPIA2 database was used to excavate the distinction in the expression of CTSG protein in non-small cell lung cancer (NSCLC) tissues versus normal non-cancerous tissues. The Ualcan database was used to compare the differences in CTSG expression at different stages of LUAD and LUSC. Immunohistochemistry (IHC) was used to detect the expression of CTSG proteins in the pathological tissues of patients with HIV-related lung cancer and patients with lung cancer without co-infection, the Kaplan-Meier method was used for survival analysis. RESULTS: We observed that CTSG expression in NSCLC is lower compared to adjacent non-tumor tissues and correlates with NSCLC clinical stage. CTSG protein expression in HIV-related lung cancer tissues was lower than in adjacent tissues and lower than in lung cancer tissues without HIV infection, with a statistically significant difference (P < 0.05). It correlated with CD4 + T cell count and CD4+/CD8 + T cell ratio, as well as with the pathological type, distant metastasis, and clinical stage of HIV-related lung cancer, all with statistical significance (P < 0.05). CONCLUSIONS: CTSG could potentially mitigate disease advancement in HIV-related lung cancer patients by inhibiting immune depletion, serving as a prospective immunotherapeutic target for both non-HIV and HIV-associated lung cancers.
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Background: PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored. Methods: In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and KaplanâMeier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RTâPCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP. Results: According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis. Conclusion: PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration.
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Lung cancer, as a malignant tumor with both high incidence and mortality in China, is one of the major causes of death in our population and one of the major public health problems in China. Effective treatment of lung cancer is a major public health task for all human beings. Angiogenesis plays an important role in the development of tumor, not only as a basic condition for tumor growth, but also as a significant factor to promote tumor metastasis. Therefore, anti-angiogenesis has become a vital means to inhibit tumor development, and anti-angiogenic drugs can rebalance pro- and anti-angiogenic factors to inhibit tumor cells. This article reviews the mechanism of blood vessel formation in tumor tissues and the mechanism of action of different anti-angiogenic drugs, the combination therapy of anti-angiogenic drugs and other anti-tumor drugs, and the mechanism of anti-angiogenic drug resistance.
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Antineoplásicos , Neoplasias Pulmonares , Neoplasias , Humanos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapia CombinadaRESUMO
Tuberculous meningitis (TBM) is the most severe and deadly manifestation of tuberculosis. Neurological complications are observed in up to 50% of patients affected. Here, attenuated Mycobacterium bovis are injected into the cerebellum of mice, and histopathological images and cultured colonies confirm successful brain infection. Then, whole-brain tissue is dissected for 10X Genomics single-cell sequencing, and we acquire 15 cell types. Transcriptional changes of inflammation processes are found in multiple cell types. Specifically, Stat1 and IRF1 are shown to mediate inflammation in macrophages and microglia. For neurons, decreased oxidative phosphorylation activity in neurons is observed, which corresponds to TBM clinical symptoms of neurodegeneration. Finally, ependymal cells present prominent transcriptional changes, and decreased FERM domain containing 4A (Frmd4a) may contribute to TBM clinical symptoms of hydrocephalus and neurodegeneration. This study shows a single-cell transcriptome of M. bovis infection in mice and improves the understanding of brain infection and neurological complications in TBM.
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Mycobacterium tuberculosis , Tuberculose Meníngea , Animais , Camundongos , Tuberculose Meníngea/complicações , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/microbiologia , Vacina BCG/efeitos adversos , Encéfalo , Inflamação/complicações , Análise de Célula ÚnicaRESUMO
Mounting evidence has postulated estrogen as a contributor for lung cancer development and progression. Here, we focused on the effect of estradiol (E2) on the immune escape of non-small cell lung cancer (NSCLC). The expression of FOXO3a in NSCLC samples was screened by gene microarray and then verified using Western blot analysis in NSCLC cell lines. Interaction between E2, SIRT1, FOXO3a and PD-L1 was determined. Following ectopic expression and depletion experiments in A549 and H1435 cells, cell proliferation and killing of cytotoxic T lymphocytes (CTLs) on NSCLC cells were evaluated. Xenograft mouse models were prepared to validate the in vivo effect of E2. E2 activated SIRT1 by up-regulating the expression of ERß and thereby weakened the killing of CTLs on NSCLC cells. E2 elevated PD-L1 by up-regulating the ERß/SIRT1 axis to promote the immune escape of NSCLC cells. SIRT1 degraded FOXO3a by reducing the acetylation level of FOXO3a and increased its ubiquitination. E2 inhibited the expression of FOXO3a and elevated PD-L1 expression, thereby promoting the immune escape of NSCLC cells. In vivo results showed that E2 facilitated the growth and metastasis of NSCLC cells in nude mice by elevating ERß via SIRT1/FOXO3a/PD-L1 axis. In summary, our data revealed the critical roles of E2/ERß/SIRT1/FOXO3a/PD-L1 axis in the immune escape of NSCLC cells and suggested that the axis may be promising therapeutic targets for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Estradiol/farmacologia , Estradiol/uso terapêutico , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Camundongos Nus , Sirtuína 1/genética , Sirtuína 1/metabolismoRESUMO
According to the existing data, the incidence and prevalence of non-tuberculous mycobacteria (NTM) are increasing worldwide. The risk factors and mental health status of patients with NTM lung disease are important and deserve our attention. A total of 180 patients with NTM lung disease hospitalized from January 2018 to December 2021 were selected as the NTM group, and 90 patients with non-severe community-acquired pneumonia (CAP) who were hospitalized during the same period were selected as the control group. The Symptom Checklist-90 (SCL-90) was used to assess the mental health status of the patients. The data were analyzed using descriptive statistics, logistic regression, and receiver operating characteristic (ROC) curves. There were no significant differences in age, sex, marital status, or smoking history between the two groups (p > 0.05), but there were significant differences in educational level, underlying diseases, occupation, living environment, and body mass index (BMI) (p < 0.01). According to the classification of basic diseases, bronchiectasis was found in 82 (45.6%) patients, followed by hypertension in 66 (36.7%) patients, and chronic obstructive pulmonary disease (COPD) in 39 (21.7%) patients. The NTM strains were identified M. intercelleulare caused 41 cases (22.8%), followed by Mycobacterium avium and Mycobacterium gordonae, each with 35 cases (19.4%), and Mycobacterium abscessus with 32 cases (17.8%). The SCL-90 found that 160 (88.9%) of 180 patients with NTM lung disease had developed mental health problems, among which the four highest-scoring factors were anxiety (ANX: 29.4%), depression (DEPR: 18.8%), sleep and diet (SD: 16.9%), and somatization (SOM: 11.3%). Through multivariate logistic regression analysis, it was found that educational level, underlying diseases, living environment, and BMI were independent risk factors for the occurrence of NTM lung disease (p < 0.01). The Hosmer-Lemeshow test was used to check the model's fitness. The ROC curve showed that the area under the curve (AUC) was 0.896, the sensitivity was 83.3%, and the specificity was 85.6%. Patients with NTM lung disease have many risk factors and prominent mental health problems that may require interventions during the process of clinical diagnosis and treatment.
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Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Nível de Saúde , Humanos , Pneumopatias/complicações , Pneumopatias/epidemiologia , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/etiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Estudos Retrospectivos , Fatores de RiscoRESUMO
ABSTRACT: To screen the prognosis-related autophagy genes of female lung adenocarcinoma by the transcriptome data and clinical data from The Cancer Genome Atlas (TCGA) database.In this study, screen meaningful female lung adenocarcinoma differential genes in TCGA, use univariate Cox proportional regression model to select genes related to prognosis, and establish the best risk model. In this study, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were applied for carrying out bioinformatics analysis of gene function.The gene expression and clinical data of 264 female lung adenocarcinoma patient samples were downloaded from TCGA. Twelve down-regulated genes: NRG3, DLC1, NLRC4, DAPK2, HSPB8, PPP1R15A, FOS, NRG1, PRKCQ, GRID1, MAP1LC3C, GABARAPL1. Up-regulated 15 genes: PARP1, BNIP3, P4HB, ATIC, IKBKE, ITGB4, VMP1, PTK6, EIF4EBP1, GAPDH, ATG9B, ERO1A, TMEM74, CDKN2A, BIRC5. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that these genes were significantly associated with autophagy and mitochondria (animals). Multifactor Cox analysis of autophagy-related genes showed that ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as independent prognostic indicators. According to the multivariate Cox proportional hazard regression model, there was a significant difference in the survival rate observed between the high-risk group (nâ=â124) and the low-risk group (nâ=â126) during the 10-year follow-up (Pâ<â.05). Univariate Cox analysis showed that tumor stage, T, M, and N stages, and risk score were all related to the survival rate of female lung adenocarcinoma patients. Multivariate Cox analysis found that autophagy-related risk scores were independent predictors, with an area under curve (AUC) value of 0.842. At last, there is autophagy genes differentially expressed among various clinicopathological parameters: ATG4A, BAK1, CCR2, DLC1, ERO1A, FKBP1A, ITGA6.The risk score can be used as an independent prognostic indicator for female patients with lung adenocarcinoma. The autophagy genes ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as prognostic genes in female lung adenocarcinoma, which may be the targets of treatment in the future.
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Adenocarcinoma de Pulmão/genética , Autofagia/genética , Neoplasias Pulmonares/genética , Biomarcadores Tumorais , Feminino , Humanos , Prognóstico , Taxa de SobrevidaRESUMO
The number of patients with chronic liver disease (CLD) is large. The social and economic burdens due to CLD have increased. The mental health problems of patients with CLD are prominent and deserve our attention and care. This study analyzed 320 patients with CLD who were hospitalized between January 2018 and January 2020. Questionnaire surveys were used to assess mental health status, including the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Symptom Checklist-90 (SCL-90). At the same time, basic data and potential related factors were collected. Data were analyzed using descriptive statistics and logistic regression. Among the 320 patients with CLD, 240 (75%) had mental health problems; among the total patients, education levels, occupations, course of disease, annual hospitalizations, complications, and nursing satisfaction were significantly different between the two groups (p < .05). The education levels and occupations of the group without mental health problems were significantly different within the group (p < .05). The SCL-90 found that the four factors with the highest scores were anxiety (ANX: 33.3%), depression (DEPR: 20.4%), somatization (SOM: 12.9%), and sleep and diet (SD: 9.6%). Logistic regression analysis showed that education levels, course of disease, annual hospitalizations, complications, and nursing satisfaction levels were independent risk factors for the mental health of patients with CLD. Model fitness was checked using the Hosmer-Lemeshow test. The receiver operating characteristic (ROC) curve showed that the area under the curve was 0.84. Patients with CLD have prominent mental health problems and experience many risk factors. It is necessary to adopt individualized psychological interventions and care to improve the quality of life of these patients.
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Hepatopatias , Saúde Mental , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Depressão/diagnóstico , Humanos , Pacientes Internados , Hepatopatias/epidemiologia , Qualidade de Vida , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Lung cancer is the leading cause of cancer-related deaths worldwide. Despite significant advances in cancer research and treatment, the overall prognosis of lung cancer patients remains poor. Therefore, the identification for novel therapeutic targets is critical for the diagnosis and treatment of lung cancer. CPNEs (copines) are a family of membrane-bound proteins that are highly conserved, soluble, ubiquitous, calcium dependent in a variety of eukaryotes. Emerging evidences have also indicated CPNE family members are involved in cancer development and progression as well. However, the expression patterns and clinical roles in cancer have not yet been well understood. In this review, we summarize recent advances concerning CPNE family members and provide insights into new potential mechanism involved in cancer development.
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Circular RNAs (circRNAs) are known to be closely involved in various diseases progression. Nevertheless, their function and underlying mechanisms in tuberculosis (TB) remain largely unknown. The aim of the present study was to explore their potential diagnostic values in TB. We downloaded the gene expression datasets of circRNA (GSE117563 and GSE106953), microRNA (miRNA, dataset GSE29190) and mRNA (GSE54992) from Gene Expression Omnibus (GEO) database. A competing endogenous RNAs (ceRNA) network was constructed based on circRNA-miRNA-mRNA potential interaction. We also constructed a circRNA-miRNA-hub gene regulatory module by using the Cytohubba. Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict their biological functions. By further validation, the expression level of hsa_circ_0028883 and hsa-miR-409-5p were detected by qRT-PCR in 20 active TB patients and 20 healthy donors. Then, Receiver Operating Characteristic (ROC) was constructed to evaluate the diagnostic values of hsa_circ_0028883. 1 differentially expressed circRNA (DE-circRNA), 1 differentially expressed miRNA (DE-miRNA), and 44 differentially expressed mRNAs (DE-mRNAs) were selected for the construction of ceRNA network in TB. A circRNA-miRNA-hub gene (mRNA) sub-network was constructed based on 1 DE-circRNA, 1 DE-miRNA, and 8 DE-mRNAs. Hsa_circ_0028883/hsa-miR-409-5p/mRNA interactions may provide some novel mechanisms for active TB. GO and KEGG pathway analysis indicated the possible function of hsa_circ_0028883 with TB. ROC analysis revealed that hsa_circ_0028883 had potential value for TB diagnosis. Hsa_circ_0028883 is a potentially reliable biomarker to diagnose active TB, but there remains a need to further study the mechanism in TB.
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MicroRNAs/genética , Tuberculose/genética , Biomarcadores , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , RNA Circular/genética , RNA Mensageiro/genética , Curva ROC , Reprodutibilidade dos Testes , Tuberculose/diagnósticoRESUMO
Purpose: Lung cancer is the most common malignancy with poor 5-year survival among men and women. Previous studies have shown that CPNE1 is up-regulated in non-small cell lung cancer (NSCLC). However, whether and how CPNE1 expression varies between different subtypes of NSCLC remains less understood. Methods: Bioinformatical analysis and GSE19188 were selected to confirm CPNE1 expression in different subtypes of NSCLC. Four microRNA prediction websites and GSE53883, GSE43000 were used to evaluate the possible targeting microRNAs. Kaplan-Meier survival curves were drawn based on Tumor Lung Bild -114 dataset using R2, UCSC Xena browser or linkedomics platform. Furthermore, we verified our prediction via qRT-PCR, and western blot and luciferase reporter assays. Results: we demonstrated that higher CPNE1 expression was associated with poorer survival in NSCLC patients. Moreover, among the different subtypes, patients with squamous cell lung cancer (SCC) exhibited higher level of CPNE1 expression, as well as substantially poorer survival. MiR-195-5p was down-regulated in NSCLC tissues. Interestingly, SCC patients showed lower miR-195-5p expression compared to patients with lung adenocarcinoma (ADC). In addition, functional assays proved that miR-195-5p overexpression inhibited the proliferation, migration, and invasion of NSCLC-derived cells by directly targeting CPNE1. Pathway analysis showed decreased expression of p-AKT, p-Erk, and Snail after transfection with miR-195-5p mimics in both lung adenocarcinoma and squamous cell lines. Conclusion: Our findings suggested that miR-195-5p regulation contributed to the differential expression of CPNE1 in NSCLC subtypes.
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Spatial data with covariate measurement errors have been commonly observed in public health studies. Existing work mainly concentrates on parameter estimation using Gibbs sampling, and no work has been conducted to understand and quantify the theoretical impact of ignoring measurement error on spatial data analysis in the form of the asymptotic biases in regression coefficients and variance components when measurement error is ignored. Plausible implementations, from frequentist perspectives, of maximum likelihood estimation in spatial covariate measurement error models are also elusive. In this paper, we propose a new class of linear mixed models for spatial data in the presence of covariate measurement errors. We show that the naive estimators of the regression coefficients are attenuated while the naive estimators of the variance components are inflated, if measurement error is ignored. We further develop a structural modeling approach to obtaining the maximum likelihood estimator by accounting for the measurement error. We study the large sample properties of the proposed maximum likelihood estimator, and propose an EM algorithm to draw inference. All the asymptotic properties are shown under the increasing-domain asymptotic framework. We illustrate the method by analyzing the Scottish lip cancer data, and evaluate its performance through a simulation study, all of which elucidate the importance of adjusting for covariate measurement errors.
RESUMO
It is well-known that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor which negatively regulates PI3K/AKT signaling and is activated widely in non-small cell lung cancers (NSCLC). However, genetic alterations in PTEN genes are rare, suggesting an undefined mechanism(s) for their suppression. Notably, growing evidence indicates that PTEN can be regulated by microRNAs involved in cancer progression. In this study, we discover that the miR-4286 is overexpressed in NSCLC and negatively regulates the expression of PTEN. Furthermore, we found that miR-4286 reduces PTEN expression by directly binding to PTEN 3'-untranslated region (UTR), thereby inhibiting NSCLC cell proliferation and mobility. Moreover, mechanistic investigations revealed that miR-4286 overexpression was a result of PTEN-mediated activation of the PI3K/AKT pathway. Taken together, our findings elucidate that miR-4286 promotes the tumorigenesis of NSCLC by interacting with PTEN. This miR-4286-mediated upregulation of PTEN might lead to new therapeutic strategies for NSCLC.